SRX1522124 GSM2033102 SRP068227 SRS1240129 GSM2033102 ChIP-Seq GENOMIC ChIP HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033102 GEO Accession GSM2033102 SRX1522125 GSM2033103 SRP068227 SRS1240127 GSM2033103 ChIP-Seq GENOMIC ChIP HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033103 GEO Accession GSM2033103 SRX1522126 GSM2033104 SRP068227 SRS1240128 GSM2033104 ChIP-Seq GENOMIC ChIP HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033104 GEO Accession GSM2033104 SRX1522127 GSM2033105 SRP068227 SRS1240126 GSM2033105 ChIP-Seq GENOMIC ChIP HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033105 GEO Accession GSM2033105 SRX1522128 GSM2033106 SRP068227 SRS1240125 GSM2033106 ChIP-Seq GENOMIC ChIP HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033106 GEO Accession GSM2033106 SRX1522129 GSM2033107 SRP068227 SRS1240124 GSM2033107 RNA-Seq TRANSCRIPTOMIC cDNA HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033107 GEO Accession GSM2033107 SRX1522130 GSM2033108 SRP068227 SRS1240123 GSM2033108 RNA-Seq TRANSCRIPTOMIC cDNA HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033108 GEO Accession GSM2033108 SRX1522131 GSM2033109 SRP068227 SRS1240122 GSM2033109 RNA-Seq TRANSCRIPTOMIC cDNA HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033109 GEO Accession GSM2033109 SRX1522132 GSM2033110 SRP068227 SRS1240121 GSM2033110 RNA-Seq TRANSCRIPTOMIC cDNA HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033110 GEO Accession GSM2033110 SRX1522133 GSM2033111 SRP068227 SRS1240120 GSM2033111 RNA-Seq TRANSCRIPTOMIC cDNA HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033111 GEO Accession GSM2033111 SRX1522134 GSM2033112 SRP068227 SRS1240119 GSM2033112 OTHER TRANSCRIPTOMIC other HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033112 GEO Accession GSM2033112 SRX1522135 GSM2033113 SRP068227 SRS1240118 GSM2033113 OTHER TRANSCRIPTOMIC other HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033113 GEO Accession GSM2033113 SRX1522136 GSM2033114 SRP068227 SRS1240117 GSM2033114 OTHER TRANSCRIPTOMIC other HeLa cells were crosslinked with 2mM DSG in PBS for 30 min at room temperature, followed by treatment with 1% formaldehyde for 15 min. After quenching with glycine, the cells were harvested and digested by Mnase (NEB, M0247S，0.5u/1000 cells) at 37°c for 20mins to produce soluble chromatin with DNA fragments in the range of 150–300 bp. This chromatin was immunoprecipitated using antibodies against RPA1 or RPA2 overnight. Then, chromatin complexes were incubated with protein G beads for 3 h. After extensive washing steps, the DNA was recovered from the protein G complex using elution buffer (10 mM Tris at pH 8.0, 10 mM EDTA at pH 8.0, 1% SDS, 150 mM NaCL, 5 mM DTT). DNA was subsequently purified using Qiagen Mini Elute PCR purification kit. For RNA-seq, total RNA was extracted using the miRNeasy Mini kit (Qiagen, Valencia, CA). For Bru-seq, bromouridine labeling, isolation of Bru-RNA and strand specific cDNA library preparation were performed as described previously (Paulsen et al., 2014; Paulsen et al., 2013). Briefly, Bromouridine (Aldrich) was added to the media of HeLa cell to a final concentration of 2 mM, and cells were incubated at 37 °C for 30 min. Cells were then directly lysed by Trizol and isolated total RNA. Then Bru-labeled RNA was isolated from the total RNA by incubation with anti-BrdU antibodies (BD Biosciences) conjugated to magnetic beads under gentle agitation at room temperature for 1 h. ChIP-seq libraries were prepared from 10 ng ChIP and input DNA using the Ovation ultralow DR Multiplex kit (NuGEN, San Carlos, CA). The ChIP-seq libraries were sequenced to 51 base pairs from both ends on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility.RNA-seq libraries were prepared with ovation RNA-seq system v2 kit (NuGEN) according to the manufacture’s instruction, and were sequenced on an Illumina HiSeq 2000 instrument in the Mayo Clinic Center for Individualized Medicine Medical Genomics Facility. For Bru-seq, Isolated Bru-labeled RNA was used to prepare strand-specific DNA libraries by using the Illumina Tru Seq Kit (Illumina) according to the manufacturer’s instructions with modifications described as (Paulsen et al., 2014). Illumina HiSeq 2000 gds 302033114 GEO Accession GSM2033114