R loops regulate promoter-proximal chromatin architecture and cellular differentiation
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ABSTRACT:
PROVIDER: PRJNA280332 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1952440.fastq.gz | Fastqsanger.gz | |||
| SRR1952450.fastq.gz | Fastqsanger.gz | |||
| SRR1952540.fastq.gz | Fastqsanger.gz | |||
| SRR1952441.fastq.gz | Fastqsanger.gz | |||
| SRR1952451.fastq.gz | Fastqsanger.gz |
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Project description:Numerous chromatin-remodeling factors are regulated by interactions with RNA, although the contexts and functions of RNA binding are poorly understood. Here we show that R loops, RNA-DNA hybrids consisting of nascent transcripts hybridized to template DNA, modulate the binding of two key chromatin-regulatory complexes, Tip60-p400 and polycomb repressive complex 2 (PRC2) in mouse embryonic stem cells (ESCs). Like PRC2, the Tip60-p400 histone acetyltransferase complex binds to nascent transcripts; however, transcription promotes chromatin binding of Tip60-p400 but not PRC2. Interestingly, we observed higher Tip60-p400 and lower PRC2 levels at genes marked by promoter-proximal R loops. Furthermore, disruption of R loops broadly decreased Tip60-p400 occupancy and increased PRC2 occupancy genome wide. In agreement with these alterations, ESCs partially depleted of R loops exhibited impaired differentiation. These results show that R loops act both positively and negatively in modulating the recruitment of key pluripotency regulators.
| S-EPMC4677832 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-09-30 | GSE67584 | GEO
Project description:Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity.
2015-09-30 | GSE67581 | GEO
Project description:Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity.
2015-09-30 | GSE67583 | GEO
Project description:Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity.
2015-09-30 | GSE67582 | GEO
Project description:Numerous chromatin-remodelling factors are regulated by interactions with RNA. However, the contexts in which chromatin-remodelling factors encounter various RNA species, as well as the molecular functions of RNA binding, are poorly understood. Here we show that R-loops, RNA:DNA hybrids consisting of nascent transcripts hybridized to template DNA strands, facilitate embryonic stem cell (ESC) differentiation by modulating the binding of two key chromatin-remodelling enzymes near gene promoters. As previously shown for polycomb repressive complex 2 (PRC2)1-5, we find that the Tip60-p400 histone acetyltransferase and nucleosome-remodelling complex binds in cis to nascent transcripts. However, whereas chromatin binding by PRC2 is broadly inhibited by transcription6, transcription is necessary for maximal Tip60-p400 binding at most target loci. Given that nascent transcripts expressed from GC-rich promoters frequently form R-loops7, we mapped the genomic locations of R-loops in mouse ESCs, observing higher average Tip60-p400 levels and lower average PRC2 levels at genes with R-loops near their transcription start sites (TSSs). Disruption of R-loops by overexpression of RNaseH1 broadly reduced Tip60-p400 and increased PRC2 enrichment, demonstrating R-loops exert both positive and negative effects on chromatin association by regulatory factors. Consistent with these findings, RNaseH1 overexpression results in widespread changes in gene expression and inhibits ESC differentiation, allowing undifferentiated cells to persist for at least two weeks after differentiation is induced. These results define a novel mechanism by which promoter-proximal R-loops modulate chromatin structure to facilitate changes in cellular identity.
2015-09-30 | GSE67580 | GEO
Project description:The highly conserved histone chaperone FACT (Facilitates Chromatin Transcription) is thought to contribute to the disassembly and reassembly of nucleosomes in the wake of RNA Polymerase II (Pol II) passage through chromatin. However, FACT’s roles in chromatin biology and transcriptional regulation in vivo in higher eukaryotes are not well understood. Here, we report that depletion of FACT leads to a reduction in the duration of promoter-proximal pausing by Pol II in Drosophila S2 cells. In addition, FACT depletion leads to a modest decrease in the occupancy of histone H3, and to decrease in occupancy of histone H2A.v in promoter-proximal nucleosomes. Finally, we observed a dramatic 5’ to 3’ repositioning of the co-transcriptionally deposited histone modifications H3K4me3 and H3K36me3 in the FACT depleted cells. Taken together, our findings are consistent with the model that FACT contributes to the interplay between chromatin architecture and control of Pol II promoter-proximal pausing.
2019-06-18 | GSE129235 | GEO
Project description:The highly conserved histone chaperone FACT (Facilitates Chromatin Transcription) is thought to contribute to the disassembly and reassembly of nucleosomes in the wake of RNA Polymerase II (Pol II) passage through chromatin. However, FACT’s roles in chromatin biology and transcriptional regulation in vivo in higher eukaryotes are not well understood. Here, we report that depletion of FACT leads to a reduction in the duration of promoter-proximal pausing by Pol II in Drosophila S2 cells. In addition, FACT depletion leads to a modest decrease in the occupancy of histone H3, and to decrease in occupancy of histone H2A.v in promoter-proximal nucleosomes. Finally, we observed a dramatic 5’ to 3’ repositioning of the co-transcriptionally deposited histone modifications H3K4me3 and H3K36me3 in the FACT depleted cells. Taken together, our findings are consistent with the model that FACT contributes to the interplay between chromatin architecture and control of Pol II promoter-proximal pausing.
2019-06-18 | GSE113470 | GEO
Project description:Drosophila FACT Regulates Promoter Proximal Pol II Pausing and Chromatin Architecture [ChIP-seq]
| PRJNA451204 | ENA
Project description:Drosophila FACT Regulates Promoter Proximal Pol II Pausing and Chromatin Architecture [RNA-seq]
| PRJNA530570 | ENA