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P300/CBP sustains Polycomb silencing by non-enzymatic functions

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Drosophila melanogaster

PROVIDER: GSE186723 | GEO | 2022/10/06

REPOSITORIES: GEO

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p300/CBP sustains Polycomb silencing by non-enzymatic functions (ChIP-seq on inhibitor-treated mouse ES cells)

Project description:Maintenance of appropriate cell states involves epigenetic mechanisms, including Polycomb group (PcG)-mediated transcriptional repression. While PcG proteins are known to induce chromatin compaction, how PcG proteins gain access to DNA in compact chromatin to achieve long-term silencing is poorly understood. Here we show that the p300/CBP co-activator is associated with two-thirds of PcG-regions and required for PcG occupancy at many of these in Drosophila and mouse cells. CBP stabilizes RNA polymerase II (Pol II) at PcG-bound repressive sites and promotes Pol II pausing independently of its histone acetyltransferase activity. CBP and Pol II pausing are necessary for RNA-DNA hybrid (R-loop) formation and nucleosome depletion at Polycomb Response Elements (PREs), whereas transcription beyond the pause region is not. These results suggest that non-enzymatic activities of the CBP co-activator have been repurposed to support PcG-mediated silencing, revealing how chromatin regulator interplay maintains transcriptional states.

2022-10-06 | GSE186722 | GEO

p300/CBP sustains Polycomb silencing by non-enzymatic functions (ChIP-seq on RNAi-treated Drosophila S2 cells)

2022-10-06 | GSE186721 | GEO

p300/CBP sustains Polycomb silencing by non-enzymatic functions (ATAC-seq on inhibitor-treated Drosophila S2 cells)

2022-10-06 | GSE186720 | GEO

p300/CBP sustains Polycomb silencing by non-enzymatic functions (RNA-seq on inhibitor-treated Drosophila S2 cells)

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p300/CBP sustains Polycomb silencing by non-enzymatic functions (ChIP-seq on inhibitor-treated Drosophila S2 cells)

2022-10-06 | GSE173473 | GEO

SENP3 and USP7 regulate Polycomb-rixosome interactions and silencing functions

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-08 | GSE197030 | GEO

CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing.

Project description:Trimethylation of histone H3 lysine 27 (H3K27me3) by Polycomb repressive complex 2 (PRC2) is essential for transcriptional silencing of Polycomb target genes, whereas acetylation of H3K27 (H3K27ac) has recently been shown to be associated with many active mammalian genes. The Trithorax protein (TRX), which associates with the histone acetyltransferase CBP, is required for maintenance of transcriptionally active states and antagonizes Polycomb silencing, although the mechanism underlying this antagonism is unknown. Here we show that H3K27 is specifically acetylated by Drosophila CBP and its deacetylation involves RPD3. H3K27ac is present at high levels in early embryos and declines after 4 hours as H3K27me3 increases. Knockdown of E(Z) decreases H3K27me3 and increases H3K27ac in bulk histones and at the promoter of the repressed Polycomb target gene abd-A, suggesting that these indeed constitute alternative modifications at some H3K27 sites. Moderate overexpression of CBP in vivo causes a global increase in H3K27ac and a decrease in H3K27me3, and strongly enhances Polycomb mutant phenotypes. We also show that TRX is required for H3K27 acetylation. TRX overexpression also causes an increase in H3K27ac and a concomitant decrease in H3K27me3 and leads to defects in Polycomb silencing. Chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) analysis reveals that H3K27ac and H3K27me3 are mutually exclusive and that H3K27ac and H3K4me3 signals coincide at most sites. We propose that TRX-dependent acetylation of H3K27 by CBP prevents H3K27me3 at Polycomb target genes and constitutes a key part of the molecular mechanism by which TRX antagonizes or prevents Polycomb silencing.

| S-EPMC2730368 | biostudies-literature

CBP/P300 Function in Repression as well as Activation Regulated by Adenovirus Small E1A

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-08-15 | E-GEOD-59693 | biostudies-arrayexpress

Hematopoietic transcription factors and p300/CBP shape the effects of BET bromodomain inhibition in leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-05-01 | E-GEOD-66123 | biostudies-arrayexpress

General transcription factor TAF4 antagonizes epigenetic silencing by Polycomb to maintain intestine stem cell functions

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-05 | GSE205442 | GEO