SRX12729048 GSM5646436 SRP342595 SRS10677427 GSM5646436 OTHER GENOMIC other MII oocytes were collected 14-15 hours after hCG injection. For mammalian gDNA samples of n sperm, 50-100 ng of purified gDNA was combined with 100 pg of each phage spike-ins to a total volume of 130 μl. For mouse MII oocytes, 10 pg of each phage spike-ins were added to the digested gDNA to a total volume of 130 μl. Then, each sample was sheared to ~200 bp by using Covaris M220 sonicator and purified once using 1× Ampure XP beads (Beckman coulter, Cat# A63882). Next, gDNA was modified using UDP-glucose and T4 Phage β-glucosyltransferase (New England Biolabs, Cat# M0357) in a total volume of 20 µl at 37 °C for 1 h. After incubation, add 5 µl of freshly prepared 0.1 N NaOH (Sigma-Aldrich, Cat# 795429) to the 20 µl of modified gDNA to denaturation at 55 °C for 10 min. Then, quickly add 1 µl of APOBEC (New England Biolabs, Cat# E7125), 1 µl of BSA and 10 µl of APOBEC Reaction Buffer to the denatured gDNA in a total volume of 100 μl. Incubate at 37 °C for 3hrs to deamination. After deamination, purify the sample once using 1× Ampure XP beads before library construction according to the TAILS procedure. HiSeq X Ten gds 305646436 GSM5646436 GEO Accession GSM5646436 SRX12729049 GSM5646437 SRP342595 SRS10677428 GSM5646437 OTHER GENOMIC other MII oocytes were collected 14-15 hours after hCG injection. For mammalian gDNA samples of n sperm, 50-100 ng of purified gDNA was combined with 100 pg of each phage spike-ins to a total volume of 130 μl. For mouse MII oocytes, 10 pg of each phage spike-ins were added to the digested gDNA to a total volume of 130 μl. Then, each sample was sheared to ~200 bp by using Covaris M220 sonicator and purified once using 1× Ampure XP beads (Beckman coulter, Cat# A63882). Next, gDNA was modified using UDP-glucose and T4 Phage β-glucosyltransferase (New England Biolabs, Cat# M0357) in a total volume of 20 µl at 37 °C for 1 h. After incubation, add 5 µl of freshly prepared 0.1 N NaOH (Sigma-Aldrich, Cat# 795429) to the 20 µl of modified gDNA to denaturation at 55 °C for 10 min. Then, quickly add 1 µl of APOBEC (New England Biolabs, Cat# E7125), 1 µl of BSA and 10 µl of APOBEC Reaction Buffer to the denatured gDNA in a total volume of 100 μl. Incubate at 37 °C for 3hrs to deamination. After deamination, purify the sample once using 1× Ampure XP beads before library construction according to the TAILS procedure. HiSeq X Ten gds 305646437 GSM5646437 GEO Accession GSM5646437 SRX12729050 GSM5646438 SRP342595 SRS10677426 GSM5646438 OTHER GENOMIC other MII oocytes were collected 14-15 hours after hCG injection. For mammalian gDNA samples of n sperm, 50-100 ng of purified gDNA was combined with 100 pg of each phage spike-ins to a total volume of 130 μl. For mouse MII oocytes, 10 pg of each phage spike-ins were added to the digested gDNA to a total volume of 130 μl. Then, each sample was sheared to ~200 bp by using Covaris M220 sonicator and purified once using 1× Ampure XP beads (Beckman coulter, Cat# A63882). Next, gDNA was modified using UDP-glucose and T4 Phage β-glucosyltransferase (New England Biolabs, Cat# M0357) in a total volume of 20 µl at 37 °C for 1 h. After incubation, add 5 µl of freshly prepared 0.1 N NaOH (Sigma-Aldrich, Cat# 795429) to the 20 µl of modified gDNA to denaturation at 55 °C for 10 min. Then, quickly add 1 µl of APOBEC (New England Biolabs, Cat# E7125), 1 µl of BSA and 10 µl of APOBEC Reaction Buffer to the denatured gDNA in a total volume of 100 μl. Incubate at 37 °C for 3hrs to deamination. After deamination, purify the sample once using 1× Ampure XP beads before library construction according to the TAILS procedure. HiSeq X Ten gds 305646438 GSM5646438 GEO Accession GSM5646438 SRX12729051 GSM5646439 SRP342595 SRS10677425 GSM5646439 OTHER GENOMIC other MII oocytes were collected 14-15 hours after hCG injection. For mammalian gDNA samples of n sperm, 50-100 ng of purified gDNA was combined with 100 pg of each phage spike-ins to a total volume of 130 μl. For mouse MII oocytes, 10 pg of each phage spike-ins were added to the digested gDNA to a total volume of 130 μl. Then, each sample was sheared to ~200 bp by using Covaris M220 sonicator and purified once using 1× Ampure XP beads (Beckman coulter, Cat# A63882). Next, gDNA was modified using UDP-glucose and T4 Phage β-glucosyltransferase (New England Biolabs, Cat# M0357) in a total volume of 20 µl at 37 °C for 1 h. After incubation, add 5 µl of freshly prepared 0.1 N NaOH (Sigma-Aldrich, Cat# 795429) to the 20 µl of modified gDNA to denaturation at 55 °C for 10 min. Then, quickly add 1 µl of APOBEC (New England Biolabs, Cat# E7125), 1 µl of BSA and 10 µl of APOBEC Reaction Buffer to the denatured gDNA in a total volume of 100 μl. Incubate at 37 °C for 3hrs to deamination. After deamination, purify the sample once using 1× Ampure XP beads before library construction according to the TAILS procedure. HiSeq X Ten gds 305646439 GSM5646439 GEO Accession GSM5646439 SRX12847066 GSM5662815 SRP342595 PRJNA773493 SRS10790598 GSM5662815 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662815 GSM5662815 GEO Accession GSM5662815 SRX12847067 GSM5662816 SRP342595 PRJNA773493 SRS10790599 GSM5662816 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662816 GSM5662816 GEO Accession GSM5662816 SRX12847068 GSM5662817 SRP342595 PRJNA773493 SRS10790600 GSM5662817 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662817 GSM5662817 GEO Accession GSM5662817 SRX12847069 GSM5662818 SRP342595 PRJNA773493 SRS10790602 GSM5662818 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662818 GSM5662818 GEO Accession GSM5662818 SRX12847070 GSM5662819 SRP342595 PRJNA773493 SRS10790603 GSM5662819 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662819 GSM5662819 GEO Accession GSM5662819 SRX12847071 GSM5662820 SRP342595 PRJNA773493 SRS10790604 GSM5662820 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662820 GSM5662820 GEO Accession GSM5662820 SRX12847072 GSM5662821 SRP342595 PRJNA773493 SRS10790605 GSM5662821 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662821 GSM5662821 GEO Accession GSM5662821 SRX12847073 GSM5662822 SRP342595 PRJNA773493 SRS10790606 GSM5662822 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662822 GSM5662822 GEO Accession GSM5662822 SRX12847074 GSM5662823 SRP342595 PRJNA773493 SRS10790607 GSM5662823 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662823 GSM5662823 GEO Accession GSM5662823 SRX12847075 GSM5662824 SRP342595 PRJNA773493 SRS10790608 GSM5662824 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662824 GSM5662824 GEO Accession GSM5662824 SRX12847076 GSM5662825 SRP342595 PRJNA773493 SRS10790609 GSM5662825 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662825 GSM5662825 GEO Accession GSM5662825 SRX12847077 GSM5662826 SRP342595 PRJNA773493 SRS10790610 GSM5662826 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662826 GSM5662826 GEO Accession GSM5662826 SRX12847078 GSM5662827 SRP342595 PRJNA773493 SRS10790611 GSM5662827 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662827 GSM5662827 GEO Accession GSM5662827 SRX12847079 GSM5662828 SRP342595 PRJNA773493 SRS10790612 GSM5662828 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662828 GSM5662828 GEO Accession GSM5662828 SRX12847080 GSM5662829 SRP342595 PRJNA773493 SRS10790613 GSM5662829 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662829 GSM5662829 GEO Accession GSM5662829 SRX12847081 GSM5662830 SRP342595 PRJNA773493 SRS10790614 GSM5662830 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662830 GSM5662830 GEO Accession GSM5662830 SRX12847082 GSM5662831 SRP342595 PRJNA773493 SRS10790615 GSM5662831 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662831 GSM5662831 GEO Accession GSM5662831 SRX12847083 GSM5662832 SRP342595 PRJNA773493 SRS10790616 GSM5662832 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662832 GSM5662832 GEO Accession GSM5662832 SRX12847084 GSM5662833 SRP342595 PRJNA773493 SRS10790617 GSM5662833 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662833 GSM5662833 GEO Accession GSM5662833 SRX12847085 GSM5662834 SRP342595 PRJNA773493 SRS10790618 GSM5662834 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662834 GSM5662834 GEO Accession GSM5662834 SRX12847086 GSM5662835 SRP342595 PRJNA773493 SRS10790619 GSM5662835 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662835 GSM5662835 GEO Accession GSM5662835 SRX12847087 GSM5662836 SRP342595 PRJNA773493 SRS10790620 GSM5662836 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662836 GSM5662836 GEO Accession GSM5662836 SRX12847088 GSM5662837 SRP342595 PRJNA773493 SRS10790621 GSM5662837 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662837 GSM5662837 GEO Accession GSM5662837 SRX12847089 GSM5662838 SRP342595 PRJNA773493 SRS10790622 GSM5662838 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662838 GSM5662838 GEO Accession GSM5662838 SRX12847090 GSM5662839 SRP342595 PRJNA773493 SRS10790623 GSM5662839 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662839 GSM5662839 GEO Accession GSM5662839 SRX12847091 GSM5662840 SRP342595 PRJNA773493 SRS10790624 GSM5662840 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662840 GSM5662840 GEO Accession GSM5662840 SRX12847092 GSM5662841 SRP342595 PRJNA773493 SRS10790625 GSM5662841 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662841 GSM5662841 GEO Accession GSM5662841 SRX12847093 GSM5662842 SRP342595 PRJNA773493 SRS10790626 GSM5662842 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662842 GSM5662842 GEO Accession GSM5662842 SRX12847094 GSM5662843 SRP342595 PRJNA773493 SRS10790627 GSM5662843 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662843 GSM5662843 GEO Accession GSM5662843 SRX12847095 GSM5662844 SRP342595 PRJNA773493 SRS10790628 GSM5662844 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662844 GSM5662844 GEO Accession GSM5662844 SRX12847096 GSM5662845 SRP342595 PRJNA773493 SRS10790629 GSM5662845 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662845 GSM5662845 GEO Accession GSM5662845 SRX12847097 GSM5662846 SRP342595 PRJNA773493 SRS10790630 GSM5662846 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662846 GSM5662846 GEO Accession GSM5662846 SRX12847098 GSM5662847 SRP342595 PRJNA773493 SRS10790631 GSM5662847 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662847 GSM5662847 GEO Accession GSM5662847 SRX12847099 GSM5662848 SRP342595 PRJNA773493 SRS10790632 GSM5662848 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662848 GSM5662848 GEO Accession GSM5662848 SRX12847100 GSM5662849 SRP342595 PRJNA773493 SRS10790635 GSM5662849 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662849 GSM5662849 GEO Accession GSM5662849 SRX12847101 GSM5662850 SRP342595 PRJNA773493 SRS10790633 GSM5662850 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662850 GSM5662850 GEO Accession GSM5662850 SRX12847102 GSM5662851 SRP342595 PRJNA773493 SRS10790634 GSM5662851 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662851 GSM5662851 GEO Accession GSM5662851 SRX12847103 GSM5662852 SRP342595 PRJNA773493 SRS10790636 GSM5662852 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662852 GSM5662852 GEO Accession GSM5662852 SRX12847104 GSM5662853 SRP342595 PRJNA773493 SRS10790637 GSM5662853 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662853 GSM5662853 GEO Accession GSM5662853 SRX12847105 GSM5662854 SRP342595 PRJNA773493 SRS10790638 GSM5662854 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662854 GSM5662854 GEO Accession GSM5662854 SRX12847106 GSM5662855 SRP342595 PRJNA773493 SRS10790639 GSM5662855 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662855 GSM5662855 GEO Accession GSM5662855 SRX12847107 GSM5662856 SRP342595 PRJNA773493 SRS10790640 GSM5662856 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662856 GSM5662856 GEO Accession GSM5662856 SRX12847108 GSM5662857 SRP342595 PRJNA773493 SRS10790641 GSM5662857 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662857 GSM5662857 GEO Accession GSM5662857 SRX12847109 GSM5662858 SRP342595 PRJNA773493 SRS10790642 GSM5662858 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662858 GSM5662858 GEO Accession GSM5662858 SRX12847110 GSM5662859 SRP342595 PRJNA773493 SRS10790643 GSM5662859 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662859 GSM5662859 GEO Accession GSM5662859 SRX12847111 GSM5662860 SRP342595 PRJNA773493 SRS10790644 GSM5662860 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662860 GSM5662860 GEO Accession GSM5662860 SRX12847112 GSM5662861 SRP342595 PRJNA773493 SRS10790645 GSM5662861 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662861 GSM5662861 GEO Accession GSM5662861 SRX12847113 GSM5662862 SRP342595 PRJNA773493 SRS10790646 GSM5662862 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662862 GSM5662862 GEO Accession GSM5662862 SRX12847114 GSM5662863 SRP342595 PRJNA773493 SRS10790647 GSM5662863 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662863 GSM5662863 GEO Accession GSM5662863 SRX12847115 GSM5662864 SRP342595 PRJNA773493 SRS10790648 GSM5662864 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662864 GSM5662864 GEO Accession GSM5662864 SRX12847116 GSM5662865 SRP342595 PRJNA773493 SRS10790649 GSM5662865 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662865 GSM5662865 GEO Accession GSM5662865 SRX12847117 GSM5662866 SRP342595 PRJNA773493 SRS10790650 GSM5662866 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662866 GSM5662866 GEO Accession GSM5662866 SRX12847118 GSM5662867 SRP342595 PRJNA773493 SRS10790651 GSM5662867 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662867 GSM5662867 GEO Accession GSM5662867 SRX12847119 GSM5662868 SRP342595 PRJNA773493 SRS10790652 GSM5662868 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662868 GSM5662868 GEO Accession GSM5662868 SRX12847120 GSM5662869 SRP342595 PRJNA773493 SRS10790653 GSM5662869 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662869 GSM5662869 GEO Accession GSM5662869 SRX12847121 GSM5662870 SRP342595 PRJNA773493 SRS10790654 GSM5662870 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662870 GSM5662870 GEO Accession GSM5662870 SRX12847122 GSM5662871 SRP342595 PRJNA773493 SRS10790655 GSM5662871 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662871 GSM5662871 GEO Accession GSM5662871 SRX12847123 GSM5662872 SRP342595 PRJNA773493 SRS10790656 GSM5662872 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662872 GSM5662872 GEO Accession GSM5662872 SRX12847124 GSM5662873 SRP342595 PRJNA773493 SRS10790657 GSM5662873 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662873 GSM5662873 GEO Accession GSM5662873 SRX12847125 GSM5662874 SRP342595 PRJNA773493 SRS10790658 GSM5662874 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662874 GSM5662874 GEO Accession GSM5662874 SRX12847126 GSM5662875 SRP342595 PRJNA773493 SRS10790659 GSM5662875 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662875 GSM5662875 GEO Accession GSM5662875 SRX12847127 GSM5662876 SRP342595 PRJNA773493 SRS10790660 GSM5662876 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662876 GSM5662876 GEO Accession GSM5662876 SRX12847128 GSM5662877 SRP342595 PRJNA773493 SRS10790661 GSM5662877 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662877 GSM5662877 GEO Accession GSM5662877 SRX12847129 GSM5662878 SRP342595 PRJNA773493 SRS10790662 GSM5662878 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662878 GSM5662878 GEO Accession GSM5662878 SRX12847130 GSM5662879 SRP342595 PRJNA773493 SRS10790663 GSM5662879 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662879 GSM5662879 GEO Accession GSM5662879 SRX12847131 GSM5662880 SRP342595 PRJNA773493 SRS10790664 GSM5662880 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662880 GSM5662880 GEO Accession GSM5662880 SRX12847132 GSM5662881 SRP342595 PRJNA773493 SRS10790665 GSM5662881 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662881 GSM5662881 GEO Accession GSM5662881 SRX12847133 GSM5662882 SRP342595 PRJNA773493 SRS10790666 GSM5662882 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662882 GSM5662882 GEO Accession GSM5662882 SRX12847134 GSM5662883 SRP342595 PRJNA773493 SRS10790667 GSM5662883 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662883 GSM5662883 GEO Accession GSM5662883 SRX12847135 GSM5662884 SRP342595 PRJNA773493 SRS10790668 GSM5662884 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662884 GSM5662884 GEO Accession GSM5662884 SRX12847136 GSM5662885 SRP342595 PRJNA773493 SRS10790669 GSM5662885 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662885 GSM5662885 GEO Accession GSM5662885 SRX12847137 GSM5662886 SRP342595 PRJNA773493 SRS10790670 GSM5662886 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662886 GSM5662886 GEO Accession GSM5662886 SRX12847138 GSM5662887 SRP342595 PRJNA773493 SRS10790671 GSM5662887 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662887 GSM5662887 GEO Accession GSM5662887 SRX12847139 GSM5662888 SRP342595 PRJNA773493 SRS10790672 GSM5662888 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662888 GSM5662888 GEO Accession GSM5662888 SRX12847140 GSM5662889 SRP342595 PRJNA773493 SRS10790673 GSM5662889 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662889 GSM5662889 GEO Accession GSM5662889 SRX12847141 GSM5662890 SRP342595 PRJNA773493 SRS10790674 GSM5662890 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662890 GSM5662890 GEO Accession GSM5662890 SRX12847142 GSM5662891 SRP342595 PRJNA773493 SRS10790675 GSM5662891 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662891 GSM5662891 GEO Accession GSM5662891 SRX12847143 GSM5662892 SRP342595 PRJNA773493 SRS10790676 GSM5662892 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662892 GSM5662892 GEO Accession GSM5662892 SRX12847144 GSM5662893 SRP342595 PRJNA773493 SRS10790677 GSM5662893 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662893 GSM5662893 GEO Accession GSM5662893 SRX12847145 GSM5662894 SRP342595 PRJNA773493 SRS10790678 GSM5662894 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662894 GSM5662894 GEO Accession GSM5662894 SRX12847146 GSM5662895 SRP342595 PRJNA773493 SRS10790679 GSM5662895 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662895 GSM5662895 GEO Accession GSM5662895 SRX12847147 GSM5662896 SRP342595 PRJNA773493 SRS10790680 GSM5662896 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662896 GSM5662896 GEO Accession GSM5662896 SRX12847148 GSM5662897 SRP342595 PRJNA773493 SRS10790681 GSM5662897 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662897 GSM5662897 GEO Accession GSM5662897 SRX12847149 GSM5662898 SRP342595 PRJNA773493 SRS10790682 GSM5662898 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662898 GSM5662898 GEO Accession GSM5662898 SRX12847150 GSM5662899 SRP342595 PRJNA773493 SRS10790683 GSM5662899 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662899 GSM5662899 GEO Accession GSM5662899 SRX12847151 GSM5662900 SRP342595 PRJNA773493 SRS10790684 GSM5662900 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662900 GSM5662900 GEO Accession GSM5662900 SRX12847152 GSM5662901 SRP342595 PRJNA773493 SRS10790685 GSM5662901 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662901 GSM5662901 GEO Accession GSM5662901 SRX12847153 GSM5662902 SRP342595 PRJNA773493 SRS10790686 GSM5662902 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662902 GSM5662902 GEO Accession GSM5662902 SRX12847154 GSM5662903 SRP342595 PRJNA773493 SRS10790687 GSM5662903 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662903 GSM5662903 GEO Accession GSM5662903 SRX12847155 GSM5662904 SRP342595 PRJNA773493 SRS10790688 GSM5662904 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662904 GSM5662904 GEO Accession GSM5662904 SRX12847156 GSM5662905 SRP342595 PRJNA773493 SRS10790689 GSM5662905 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662905 GSM5662905 GEO Accession GSM5662905 SRX12847157 GSM5662906 SRP342595 PRJNA773493 SRS10790690 GSM5662906 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662906 GSM5662906 GEO Accession GSM5662906 SRX12847158 GSM5662907 SRP342595 PRJNA773493 SRS10790691 GSM5662907 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662907 GSM5662907 GEO Accession GSM5662907 SRX12847159 GSM5662908 SRP342595 PRJNA773493 SRS10790692 GSM5662908 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662908 GSM5662908 GEO Accession GSM5662908 SRX12847160 GSM5662909 SRP342595 PRJNA773493 SRS10790693 GSM5662909 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662909 GSM5662909 GEO Accession GSM5662909 SRX12847161 GSM5662910 SRP342595 PRJNA773493 SRS10790694 GSM5662910 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662910 GSM5662910 GEO Accession GSM5662910 SRX12847162 GSM5662911 SRP342595 PRJNA773493 SRS10790695 GSM5662911 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662911 GSM5662911 GEO Accession GSM5662911 SRX12847163 GSM5662912 SRP342595 PRJNA773493 SRS10790696 GSM5662912 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662912 GSM5662912 GEO Accession GSM5662912 SRX12847164 GSM5662913 SRP342595 PRJNA773493 SRS10790697 GSM5662913 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662913 GSM5662913 GEO Accession GSM5662913 SRX12847165 GSM5662914 SRP342595 PRJNA773493 SRS10790698 GSM5662914 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662914 GSM5662914 GEO Accession GSM5662914 SRX12847166 GSM5662915 SRP342595 PRJNA773493 SRS10790699 GSM5662915 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662915 GSM5662915 GEO Accession GSM5662915 SRX12847167 GSM5662916 SRP342595 PRJNA773493 SRS10790700 GSM5662916 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662916 GSM5662916 GEO Accession GSM5662916 SRX12847168 GSM5662917 SRP342595 PRJNA773493 SRS10790701 GSM5662917 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662917 GSM5662917 GEO Accession GSM5662917 SRX12847169 GSM5662918 SRP342595 PRJNA773493 SRS10790702 GSM5662918 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662918 GSM5662918 GEO Accession GSM5662918 SRX12847170 GSM5662919 SRP342595 PRJNA773493 SRS10790703 GSM5662919 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662919 GSM5662919 GEO Accession GSM5662919 SRX12847171 GSM5662920 SRP342595 PRJNA773493 SRS10790704 GSM5662920 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662920 GSM5662920 GEO Accession GSM5662920 SRX12847172 GSM5662921 SRP342595 PRJNA773493 SRS10790705 GSM5662921 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662921 GSM5662921 GEO Accession GSM5662921 SRX12847173 GSM5662922 SRP342595 PRJNA773493 SRS10790706 GSM5662922 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662922 GSM5662922 GEO Accession GSM5662922 SRX12847174 GSM5662923 SRP342595 PRJNA773493 SRS10790707 GSM5662923 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662923 GSM5662923 GEO Accession GSM5662923 SRX12847175 GSM5662924 SRP342595 PRJNA773493 SRS10790708 GSM5662924 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662924 GSM5662924 GEO Accession GSM5662924 SRX12847176 GSM5662925 SRP342595 PRJNA773493 SRS10790709 GSM5662925 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662925 GSM5662925 GEO Accession GSM5662925 SRX12847177 GSM5662926 SRP342595 PRJNA773493 SRS10790710 GSM5662926 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662926 GSM5662926 GEO Accession GSM5662926 SRX12847178 GSM5662927 SRP342595 PRJNA773493 SRS10790711 GSM5662927 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662927 GSM5662927 GEO Accession GSM5662927 SRX12847179 GSM5662928 SRP342595 PRJNA773493 SRS10790712 GSM5662928 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662928 GSM5662928 GEO Accession GSM5662928 SRX12847180 GSM5662929 SRP342595 PRJNA773493 SRS10790713 GSM5662929 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662929 GSM5662929 GEO Accession GSM5662929 SRX12847181 GSM5662930 SRP342595 PRJNA773493 SRS10790714 GSM5662930 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662930 GSM5662930 GEO Accession GSM5662930 SRX12847182 GSM5662931 SRP342595 PRJNA773493 SRS10790715 GSM5662931 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662931 GSM5662931 GEO Accession GSM5662931 SRX12847183 GSM5662932 SRP342595 PRJNA773493 SRS10790716 GSM5662932 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662932 GSM5662932 GEO Accession GSM5662932 SRX12847184 GSM5662933 SRP342595 PRJNA773493 SRS10790717 GSM5662933 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662933 GSM5662933 GEO Accession GSM5662933 SRX12847185 GSM5662934 SRP342595 PRJNA773493 SRS10790718 GSM5662934 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662934 GSM5662934 GEO Accession GSM5662934 SRX12847186 GSM5662935 SRP342595 PRJNA773493 SRS10790719 GSM5662935 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662935 GSM5662935 GEO Accession GSM5662935 SRX12847187 GSM5662936 SRP342595 PRJNA773493 SRS10790720 GSM5662936 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662936 GSM5662936 GEO Accession GSM5662936 SRX12847188 GSM5662937 SRP342595 PRJNA773493 SRS10790721 GSM5662937 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662937 GSM5662937 GEO Accession GSM5662937 SRX12847189 GSM5662938 SRP342595 PRJNA773493 SRS10790722 GSM5662938 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662938 GSM5662938 GEO Accession GSM5662938 SRX12847190 GSM5662939 SRP342595 PRJNA773493 SRS10790723 GSM5662939 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662939 GSM5662939 GEO Accession GSM5662939 SRX12847191 GSM5662940 SRP342595 PRJNA773493 SRS10790724 GSM5662940 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662940 GSM5662940 GEO Accession GSM5662940 SRX12847192 GSM5662941 SRP342595 PRJNA773493 SRS10790725 GSM5662941 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662941 GSM5662941 GEO Accession GSM5662941 SRX12847193 GSM5662942 SRP342595 PRJNA773493 SRS10790726 GSM5662942 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662942 GSM5662942 GEO Accession GSM5662942 SRX12847194 GSM5662943 SRP342595 PRJNA773493 SRS10790727 GSM5662943 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662943 GSM5662943 GEO Accession GSM5662943 SRX12847195 GSM5662944 SRP342595 PRJNA773493 SRS10790728 GSM5662944 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. ACE-seq, scBS-seq and scRNA-seq HiSeq X Ten gds 305662944 GSM5662944 GEO Accession GSM5662944 SRX13103215 GSM5685922 SRP342595 PRJNA773493 SRS11039508 GSM5685922 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685922 GSM5685922 GEO Accession GSM5685922 SRX13103216 GSM5685923 SRP342595 PRJNA773493 SRS11039509 GSM5685923 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685923 GSM5685923 GEO Accession GSM5685923 SRX13103217 GSM5685924 SRP342595 PRJNA773493 SRS11039512 GSM5685924 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685924 GSM5685924 GEO Accession GSM5685924 SRX13103218 GSM5685925 SRP342595 PRJNA773493 SRS11039511 GSM5685925 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685925 GSM5685925 GEO Accession GSM5685925 SRX13103219 GSM5685926 SRP342595 PRJNA773493 SRS11039513 GSM5685926 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685926 GSM5685926 GEO Accession GSM5685926 SRX13103220 GSM5685927 SRP342595 PRJNA773493 SRS11039514 GSM5685927 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685927 GSM5685927 GEO Accession GSM5685927 SRX13103221 GSM5685928 SRP342595 PRJNA773493 SRS11039515 GSM5685928 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685928 GSM5685928 GEO Accession GSM5685928 SRX13103222 GSM5685929 SRP342595 PRJNA773493 SRS11039516 GSM5685929 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685929 GSM5685929 GEO Accession GSM5685929 SRX13103223 GSM5685891 SRP342595 PRJNA773493 SRS11039518 GSM5685891 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685891 GSM5685891 GEO Accession GSM5685891 SRX13103224 GSM5685892 SRP342595 PRJNA773493 SRS11039517 GSM5685892 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685892 GSM5685892 GEO Accession GSM5685892 SRX13103225 GSM5685893 SRP342595 PRJNA773493 SRS11039519 GSM5685893 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685893 GSM5685893 GEO Accession GSM5685893 SRX13103226 GSM5685894 SRP342595 PRJNA773493 SRS11039520 GSM5685894 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685894 GSM5685894 GEO Accession GSM5685894 SRX13103227 GSM5685895 SRP342595 PRJNA773493 SRS11039521 GSM5685895 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685895 GSM5685895 GEO Accession GSM5685895 SRX13103228 GSM5685896 SRP342595 PRJNA773493 SRS11039522 GSM5685896 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685896 GSM5685896 GEO Accession GSM5685896 SRX13103229 GSM5685897 SRP342595 PRJNA773493 SRS11039524 GSM5685897 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685897 GSM5685897 GEO Accession GSM5685897 SRX13103230 GSM5685930 SRP342595 PRJNA773493 SRS11039523 GSM5685930 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685930 GSM5685930 GEO Accession GSM5685930 SRX13103231 GSM5685931 SRP342595 PRJNA773493 SRS11039525 GSM5685931 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685931 GSM5685931 GEO Accession GSM5685931 SRX13103232 GSM5685932 SRP342595 PRJNA773493 SRS11039526 GSM5685932 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685932 GSM5685932 GEO Accession GSM5685932 SRX13103233 GSM5685933 SRP342595 PRJNA773493 SRS11039527 GSM5685933 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685933 GSM5685933 GEO Accession GSM5685933 SRX13103234 GSM5685934 SRP342595 PRJNA773493 SRS11039528 GSM5685934 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685934 GSM5685934 GEO Accession GSM5685934 SRX13103235 GSM5685935 SRP342595 PRJNA773493 SRS11039529 GSM5685935 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685935 GSM5685935 GEO Accession GSM5685935 SRX13103236 GSM5685936 SRP342595 PRJNA773493 SRS11039530 GSM5685936 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685936 GSM5685936 GEO Accession GSM5685936 SRX13103237 GSM5685937 SRP342595 PRJNA773493 SRS11039531 GSM5685937 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685937 GSM5685937 GEO Accession GSM5685937 SRX13103238 GSM5685938 SRP342595 PRJNA773493 SRS11039532 GSM5685938 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685938 GSM5685938 GEO Accession GSM5685938 SRX13103239 GSM5685939 SRP342595 PRJNA773493 SRS11039533 GSM5685939 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685939 GSM5685939 GEO Accession GSM5685939 SRX13103240 GSM5685940 SRP342595 PRJNA773493 SRS11039534 GSM5685940 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685940 GSM5685940 GEO Accession GSM5685940 SRX13103241 GSM5685941 SRP342595 PRJNA773493 SRS11039535 GSM5685941 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685941 GSM5685941 GEO Accession GSM5685941 SRX13103242 GSM5685942 SRP342595 PRJNA773493 SRS11039536 GSM5685942 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685942 GSM5685942 GEO Accession GSM5685942 SRX13103243 GSM5685943 SRP342595 PRJNA773493 SRS11039538 GSM5685943 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685943 GSM5685943 GEO Accession GSM5685943 SRX13103244 GSM5685944 SRP342595 PRJNA773493 SRS11039537 GSM5685944 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685944 GSM5685944 GEO Accession GSM5685944 SRX13103245 GSM5685945 SRP342595 PRJNA773493 SRS11039539 GSM5685945 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685945 GSM5685945 GEO Accession GSM5685945 SRX13103246 GSM5685946 SRP342595 PRJNA773493 SRS11039540 GSM5685946 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685946 GSM5685946 GEO Accession GSM5685946 SRX13103247 GSM5685947 SRP342595 PRJNA773493 SRS11039541 GSM5685947 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685947 GSM5685947 GEO Accession GSM5685947 SRX13103248 GSM5685948 SRP342595 PRJNA773493 SRS11039542 GSM5685948 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685948 GSM5685948 GEO Accession GSM5685948 SRX13103249 GSM5685949 SRP342595 PRJNA773493 SRS11039543 GSM5685949 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685949 GSM5685949 GEO Accession GSM5685949 SRX13103250 GSM5685950 SRP342595 PRJNA773493 SRS11039545 GSM5685950 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685950 GSM5685950 GEO Accession GSM5685950 SRX13103251 GSM5685951 SRP342595 PRJNA773493 SRS11039544 GSM5685951 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685951 GSM5685951 GEO Accession GSM5685951 SRX13103252 GSM5685952 SRP342595 PRJNA773493 SRS11039546 GSM5685952 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685952 GSM5685952 GEO Accession GSM5685952 SRX13103253 GSM5685953 SRP342595 PRJNA773493 SRS11039547 GSM5685953 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685953 GSM5685953 GEO Accession GSM5685953 SRX13103254 GSM5685954 SRP342595 PRJNA773493 SRS11039548 GSM5685954 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685954 GSM5685954 GEO Accession GSM5685954 SRX13103255 GSM5685955 SRP342595 PRJNA773493 SRS11039550 GSM5685955 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685955 GSM5685955 GEO Accession GSM5685955 SRX13103256 GSM5685956 SRP342595 PRJNA773493 SRS11039549 GSM5685956 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685956 GSM5685956 GEO Accession GSM5685956 SRX13103257 GSM5685957 SRP342595 PRJNA773493 SRS11039552 GSM5685957 Bisulfite-Seq GENOMIC RANDOM To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685957 GSM5685957 GEO Accession GSM5685957 SRX13103258 GSM5685958 SRP342595 PRJNA773493 SRS11039551 GSM5685958 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685958 GSM5685958 GEO Accession GSM5685958 SRX13103259 GSM5685959 SRP342595 PRJNA773493 SRS11039553 GSM5685959 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685959 GSM5685959 GEO Accession GSM5685959 SRX13103262 GSM5685962 SRP342595 PRJNA773493 SRS11039558 GSM5685962 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685962 GSM5685962 GEO Accession GSM5685962 SRX13103263 GSM5685963 SRP342595 PRJNA773493 SRS11039556 GSM5685963 RNA-Seq TRANSCRIPTOMIC cDNA To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685963 GSM5685963 GEO Accession GSM5685963 SRX13103288 GSM5685898 SRP342595 PRJNA773493 SRS11039582 GSM5685898 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685898 GSM5685898 GEO Accession GSM5685898 SRX13103289 GSM5685899 SRP342595 PRJNA773493 SRS11039583 GSM5685899 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685899 GSM5685899 GEO Accession GSM5685899 SRX13103290 GSM5685900 SRP342595 PRJNA773493 SRS11039584 GSM5685900 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685900 GSM5685900 GEO Accession GSM5685900 SRX13103291 GSM5685901 SRP342595 PRJNA773493 SRS11039585 GSM5685901 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685901 GSM5685901 GEO Accession GSM5685901 SRX13103292 GSM5685902 SRP342595 PRJNA773493 SRS11039586 GSM5685902 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685902 GSM5685902 GEO Accession GSM5685902 SRX13103293 GSM5685903 SRP342595 PRJNA773493 SRS11039588 GSM5685903 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685903 GSM5685903 GEO Accession GSM5685903 SRX13103294 GSM5685904 SRP342595 PRJNA773493 SRS11039589 GSM5685904 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685904 GSM5685904 GEO Accession GSM5685904 SRX13103295 GSM5685905 SRP342595 PRJNA773493 SRS11039587 GSM5685905 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685905 GSM5685905 GEO Accession GSM5685905 SRX13103296 GSM5685906 SRP342595 PRJNA773493 SRS11039590 GSM5685906 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685906 GSM5685906 GEO Accession GSM5685906 SRX13103297 GSM5685907 SRP342595 PRJNA773493 SRS11039592 GSM5685907 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685907 GSM5685907 GEO Accession GSM5685907 SRX13103298 GSM5685908 SRP342595 PRJNA773493 SRS11039591 GSM5685908 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685908 GSM5685908 GEO Accession GSM5685908 SRX13103299 GSM5685909 SRP342595 PRJNA773493 SRS11039593 GSM5685909 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685909 GSM5685909 GEO Accession GSM5685909 SRX13103300 GSM5685910 SRP342595 PRJNA773493 SRS11039594 GSM5685910 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685910 GSM5685910 GEO Accession GSM5685910 SRX13103301 GSM5685911 SRP342595 PRJNA773493 SRS11039595 GSM5685911 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685911 GSM5685911 GEO Accession GSM5685911 SRX13103302 GSM5685912 SRP342595 PRJNA773493 SRS11039596 GSM5685912 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685912 GSM5685912 GEO Accession GSM5685912 SRX13103303 GSM5685913 SRP342595 PRJNA773493 SRS11039597 GSM5685913 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685913 GSM5685913 GEO Accession GSM5685913 SRX13103304 GSM5685914 SRP342595 PRJNA773493 SRS11039598 GSM5685914 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685914 GSM5685914 GEO Accession GSM5685914 SRX13103305 GSM5685915 SRP342595 PRJNA773493 SRS11039599 GSM5685915 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685915 GSM5685915 GEO Accession GSM5685915 SRX13103306 GSM5685916 SRP342595 PRJNA773493 SRS11039600 GSM5685916 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685916 GSM5685916 GEO Accession GSM5685916 SRX13103307 GSM5685917 SRP342595 PRJNA773493 SRS11039601 GSM5685917 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685917 GSM5685917 GEO Accession GSM5685917 SRX13103308 GSM5685918 SRP342595 PRJNA773493 SRS11039602 GSM5685918 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685918 GSM5685918 GEO Accession GSM5685918 SRX13103309 GSM5685919 SRP342595 PRJNA773493 SRS11039603 GSM5685919 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685919 GSM5685919 GEO Accession GSM5685919 SRX13103310 GSM5685920 SRP342595 PRJNA773493 SRS11039604 GSM5685920 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685920 GSM5685920 GEO Accession GSM5685920 SRX13103311 GSM5685921 SRP342595 PRJNA773493 SRS11039605 GSM5685921 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. scBS-seq: The zona pellucida of MII oocytes and 2-cell embryos were firstly removed by Tyrode's Solution. Construction of the scBS-seq or scCOOL-seq libraries were performed as previously described (Guo et al., 2017a; Smallwood et al., 2014). DNA libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Single-cell RNA-seq: Single-cell RNA-seq of Nlrp14-/- MII oocytes and Nlrp14mat△/+ 2-cell embryos were conducted by using smart-seq2 protocol (Picelli et al., 2014), while WT controls were also included. In brief, single cell was picked into lysis buffer and Poly(A)+ RNA was captured by Oligo(dT) primer. The first strand of cDNA was synthesized by reverse transcription, then amplified, purified and fragmented. Fragmented cDNA was processed to construct RNA-seq library by NEBNext UltraII DNA Library Prep Kit for Illumina. Illumina NovaSeq 6000 gds 305685921 GSM5685921 GEO Accession GSM5685921 SRX17155176 GSM6482842 SRP342595 PRJNA773493 SRS14726911 GSM6482842 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Illumina NovaSeq 6000 gds 306482842 GSM6482842 GEO Accession GSM6482842 SRX17155177 GSM6482843 SRP342595 PRJNA773493 SRS14726912 GSM6482843 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Illumina NovaSeq 6000 gds 306482843 GSM6482843 GEO Accession GSM6482843 SRX17155178 GSM6482844 SRP342595 PRJNA773493 SRS14726913 GSM6482844 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Illumina NovaSeq 6000 gds 306482844 GSM6482844 GEO Accession GSM6482844 SRX17155179 GSM6482845 SRP342595 PRJNA773493 SRS14726914 GSM6482845 OTHER GENOMIC other To collect preimplantation embryos, 6-8week old wild-type and Nlrp14-/- females (C57BL/6) were super-ovulated by injection of PMSG and hCG. MII oocytes were collected at 14-15 hours after hCG injection. As to preimplantation embryos, superovulated female mice were mated with either C57BL/6 or PWK males. Embryos were collected at 25-26 h (zygotes), 42-43 h (2-cell), 56-57 h (4-cell), 70-71 h (8-cell), and 94-96 h (blastocysts) after hCG injection. To isolate pronuclei, mouse zygotes at PN3- PN4 stages were collected and pronucleus were isolated as previously described (Guo et al., 2014). Zygotes which were maternally deficient in Tet3 were obtained through Zp3-Cre mediated conditional knockout in oocytes as previously described (Guo et al., 2014). To inhibit DNA replication, zygotes were treated with aphidicolin until the collection of pronuclei (Guo et al., 2014). The inhibition of DNA replication in mouse zygotes was validated by EdU incorporation assay. ACE-seq: The construction of ACE-seq libraries followed the published protocol (Schutsky et al., 2018), with minor modifications. Fragmented gDNA was first modified using UDP- glucose and T4 Phage β-glucosyltransferase at 37 °C for 1 h. Then 0.1 N NaOH was added to the modified gDNA for denaturation at 55 °C for 10 min. APOBEC enzyme was used to deaminate gDNA at 37°C for 3 hrs. After deamination, gDNA was purified using Ampure XP beads before library construction according to the TAILS procedure (Gu et al., 2019; Yan et al., 2021). Finally, the ACE-seq libraries were sequenced on a Novaseq sequencer for 150 bp paired-end sequencing. Illumina NovaSeq 6000 gds 306482845 GSM6482845 GEO Accession GSM6482845