SRX10333889 GSM5170919 SRP310439 SRS8453611 GSM5170919 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170919 GSM5170919 GEO Accession GSM5170919 SRX10333890 GSM5170928 SRP310439 SRS8453610 GSM5170928 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170928 GSM5170928 GEO Accession GSM5170928 SRX10333894 GSM5170932 SRP310439 SRS8453613 GSM5170932 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170932 GSM5170932 GEO Accession GSM5170932 SRX10333895 GSM5170933 SRP310439 SRS8453615 GSM5170933 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170933 GSM5170933 GEO Accession GSM5170933 SRX10333896 GSM5170934 SRP310439 SRS8453614 GSM5170934 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170934 GSM5170934 GEO Accession GSM5170934 SRX10333897 GSM5170935 SRP310439 SRS8453617 GSM5170935 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170935 GSM5170935 GEO Accession GSM5170935 SRX10333898 GSM5170936 SRP310439 SRS8453619 GSM5170936 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170936 GSM5170936 GEO Accession GSM5170936 SRX10333899 GSM5170937 SRP310439 SRS8453618 GSM5170937 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170937 GSM5170937 GEO Accession GSM5170937 SRX10333900 GSM5170938 SRP310439 SRS8453616 GSM5170938 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170938 GSM5170938 GEO Accession GSM5170938 SRX10333901 GSM5170939 SRP310439 SRS8453623 GSM5170939 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170939 GSM5170939 GEO Accession GSM5170939 SRX10333902 GSM5170940 SRP310439 SRS8453621 GSM5170940 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170940 GSM5170940 GEO Accession GSM5170940 SRX10333903 GSM5170941 SRP310439 SRS8453620 GSM5170941 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170941 GSM5170941 GEO Accession GSM5170941 SRX10333907 GSM5170920 SRP310439 SRS8453627 GSM5170920 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170920 GSM5170920 GEO Accession GSM5170920 SRX10333908 GSM5170921 SRP310439 SRS8453625 GSM5170921 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170921 GSM5170921 GEO Accession GSM5170921 SRX10333909 GSM5170922 SRP310439 SRS8453628 GSM5170922 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170922 GSM5170922 GEO Accession GSM5170922 SRX10333910 GSM5170923 SRP310439 SRS8453630 GSM5170923 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170923 GSM5170923 GEO Accession GSM5170923 SRX10333911 GSM5170924 SRP310439 SRS8453629 GSM5170924 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170924 GSM5170924 GEO Accession GSM5170924 SRX10333912 GSM5170925 SRP310439 SRS8453631 GSM5170925 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170925 GSM5170925 GEO Accession GSM5170925 SRX10333913 GSM5170926 SRP310439 SRS8453632 GSM5170926 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170926 GSM5170926 GEO Accession GSM5170926 SRX10333914 GSM5170927 SRP310439 SRS8453633 GSM5170927 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305170927 GSM5170927 GEO Accession GSM5170927 SRX10601006 GSM5241220 SRP310439 PRJNA714104 SRS8702413 GSM5241220 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241220 GSM5241220 GEO Accession GSM5241220 SRX10601007 GSM5241221 SRP310439 PRJNA714104 SRS8702414 GSM5241221 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241221 GSM5241221 GEO Accession GSM5241221 SRX10601008 GSM5241222 SRP310439 PRJNA714104 SRS8702415 GSM5241222 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241222 GSM5241222 GEO Accession GSM5241222 SRX10601009 GSM5241223 SRP310439 PRJNA714104 SRS8702418 GSM5241223 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241223 GSM5241223 GEO Accession GSM5241223 SRX10601010 GSM5241224 SRP310439 PRJNA714104 SRS8702419 GSM5241224 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241224 GSM5241224 GEO Accession GSM5241224 SRX10601011 GSM5241225 SRP310439 PRJNA714104 SRS8702420 GSM5241225 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241225 GSM5241225 GEO Accession GSM5241225 SRX10601012 GSM5241226 SRP310439 PRJNA714104 SRS8702421 GSM5241226 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241226 GSM5241226 GEO Accession GSM5241226 SRX10601013 GSM5241227 SRP310439 PRJNA714104 SRS8702422 GSM5241227 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305241227 GSM5241227 GEO Accession GSM5241227 SRX11320583 GSM5411701 SRP310439 PRJNA714104 SRS9365597 GSM5411701 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411701 GSM5411701 GEO Accession GSM5411701 SRX11320584 GSM5411702 SRP310439 PRJNA714104 SRS9365599 GSM5411702 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411702 GSM5411702 GEO Accession GSM5411702 SRX11320585 GSM5411703 SRP310439 PRJNA714104 SRS9365601 GSM5411703 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411703 GSM5411703 GEO Accession GSM5411703 SRX11320586 GSM5411704 SRP310439 PRJNA714104 SRS9365600 GSM5411704 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411704 GSM5411704 GEO Accession GSM5411704 SRX11320587 GSM5411705 SRP310439 PRJNA714104 SRS9365602 GSM5411705 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411705 GSM5411705 GEO Accession GSM5411705 SRX11320588 GSM5411706 SRP310439 PRJNA714104 SRS9365603 GSM5411706 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411706 GSM5411706 GEO Accession GSM5411706 SRX11320589 GSM5411707 SRP310439 PRJNA714104 SRS9365604 GSM5411707 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411707 GSM5411707 GEO Accession GSM5411707 SRX11320590 GSM5411708 SRP310439 PRJNA714104 SRS9365605 GSM5411708 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411708 GSM5411708 GEO Accession GSM5411708 SRX11320591 GSM5411709 SRP310439 PRJNA714104 SRS9365607 GSM5411709 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411709 GSM5411709 GEO Accession GSM5411709 SRX11320592 GSM5411710 SRP310439 PRJNA714104 SRS9365606 GSM5411710 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411710 GSM5411710 GEO Accession GSM5411710 SRX11320593 GSM5411711 SRP310439 PRJNA714104 SRS9365608 GSM5411711 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411711 GSM5411711 GEO Accession GSM5411711 SRX11320594 GSM5411712 SRP310439 PRJNA714104 SRS9365609 GSM5411712 OTHER TRANSCRIPTOMIC other For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411712 GSM5411712 GEO Accession GSM5411712 SRX11320595 GSM5411713 SRP310439 PRJNA714104 SRS9365610 GSM5411713 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411713 GSM5411713 GEO Accession GSM5411713 SRX11320596 GSM5411714 SRP310439 PRJNA714104 SRS9365611 GSM5411714 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411714 GSM5411714 GEO Accession GSM5411714 SRX11320597 GSM5411715 SRP310439 PRJNA714104 SRS9365612 GSM5411715 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411715 GSM5411715 GEO Accession GSM5411715 SRX11320598 GSM5411716 SRP310439 PRJNA714104 SRS9365614 GSM5411716 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411716 GSM5411716 GEO Accession GSM5411716 SRX11320599 GSM5411717 SRP310439 PRJNA714104 SRS9365613 GSM5411717 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411717 GSM5411717 GEO Accession GSM5411717 SRX11320600 GSM5411718 SRP310439 PRJNA714104 SRS9365616 GSM5411718 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411718 GSM5411718 GEO Accession GSM5411718 SRX11320601 GSM5411719 SRP310439 PRJNA714104 SRS9365615 GSM5411719 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411719 GSM5411719 GEO Accession GSM5411719 SRX11320602 GSM5411720 SRP310439 PRJNA714104 SRS9365617 GSM5411720 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411720 GSM5411720 GEO Accession GSM5411720 SRX11320603 GSM5411721 SRP310439 PRJNA714104 SRS9365618 GSM5411721 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411721 GSM5411721 GEO Accession GSM5411721 SRX11320604 GSM5411722 SRP310439 PRJNA714104 SRS9365619 GSM5411722 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411722 GSM5411722 GEO Accession GSM5411722 SRX11320605 GSM5411723 SRP310439 PRJNA714104 SRS9365620 GSM5411723 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411723 GSM5411723 GEO Accession GSM5411723 SRX11320606 GSM5411724 SRP310439 PRJNA714104 SRS9365622 GSM5411724 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411724 GSM5411724 GEO Accession GSM5411724 SRX11320607 GSM5411725 SRP310439 PRJNA714104 SRS9365621 GSM5411725 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411725 GSM5411725 GEO Accession GSM5411725 SRX11320608 GSM5411726 SRP310439 PRJNA714104 SRS9365623 GSM5411726 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411726 GSM5411726 GEO Accession GSM5411726 SRX11320609 GSM5411727 SRP310439 PRJNA714104 SRS9365624 GSM5411727 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411727 GSM5411727 GEO Accession GSM5411727 SRX11320610 GSM5411728 SRP310439 PRJNA714104 SRS9365625 GSM5411728 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411728 GSM5411728 GEO Accession GSM5411728 SRX11320611 GSM5411729 SRP310439 PRJNA714104 SRS9365627 GSM5411729 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411729 GSM5411729 GEO Accession GSM5411729 SRX11320612 GSM5411730 SRP310439 PRJNA714104 SRS9365626 GSM5411730 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411730 GSM5411730 GEO Accession GSM5411730 SRX11320613 GSM5411731 SRP310439 PRJNA714104 SRS9365628 GSM5411731 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411731 GSM5411731 GEO Accession GSM5411731 SRX11320614 GSM5411732 SRP310439 PRJNA714104 SRS9365629 GSM5411732 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411732 GSM5411732 GEO Accession GSM5411732 SRX11320615 GSM5411733 SRP310439 PRJNA714104 SRS9365631 GSM5411733 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411733 GSM5411733 GEO Accession GSM5411733 SRX11320616 GSM5411734 SRP310439 PRJNA714104 SRS9365630 GSM5411734 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411734 GSM5411734 GEO Accession GSM5411734 SRX11320617 GSM5411735 SRP310439 PRJNA714104 SRS9365632 GSM5411735 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411735 GSM5411735 GEO Accession GSM5411735 SRX11320618 GSM5411736 SRP310439 PRJNA714104 SRS9365634 GSM5411736 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411736 GSM5411736 GEO Accession GSM5411736 SRX11320619 GSM5411737 SRP310439 PRJNA714104 SRS9365633 GSM5411737 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411737 GSM5411737 GEO Accession GSM5411737 SRX11320620 GSM5411738 SRP310439 PRJNA714104 SRS9365635 GSM5411738 ChIP-Seq GENOMIC ChIP For ChIP-seq in human DLD1 cells, 20-50 million cells were crosslinked with 1% paraformaldehyde (Electron Microscopy Sciences) in PBS for 10 min at r.t. Spike-in mouse embryonic fibroblast fixed cells were added to samples as described previously (Orlando et al., 2014). Chromatin was sonicated with the Covaris E220 for 4 min with 10% duty cycle, 140 peak intensity power, 200 cycles per burst. Immunoprecipitations were carried out with antibodies and Dynabeads Protein G (Invitrogen). For ChIP-seq in yeast cells, cells were fixed with 2.2% formaldehyde for 15 min. PRO-seq sample preparation was performed according to the previously described qPRO-seq protocol (Judd et al., 2020). ~5 million DLD-1 nuclei mixed with spike-in Drosophila S2 nuclei were used for nuclear run-on assay. For pulse-chase nascdnt RNA labeling with TT-seq, cells were treated with 250 nM NVP-2 for 1 h, followed by nascent RNA labeling with 500 µM 4-thiouridin (Sigma # T4509) for 15 min. For ChIP-seq, DNA libraries were prepared by the HTP Library Preparation Kit for Illimina (KAPA). For PRO-seq, adapter sequences previously described (Mahat et al., 2016) were used. PRO-seq libraries were prepared according to the previously described qPRO-seq protocol (Judd et al., 2020). TT-seq library was prepared as described previously (Schwalb et al., 2016; Rosencrance wt al., 2020). Illumina NovaSeq 6000 gds 305411738 GSM5411738 GEO Accession GSM5411738