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Status |
Public on Oct 06, 2022 |
Title |
p300/CBP sustains Polycomb silencing by non-enzymatic functions (RNA-seq on inhibitor-treated Drosophila S2 cells) |
Organism |
Drosophila melanogaster |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
RNA-seq analysis of gene expression changes in Drosophila late embryonic Schneider 2 cells treated for 30 minutes with the CBP HAT pharmacological inhibitor C646 with and without a drug washout (WO) of 1 hr or 4 hr, relative to untreated cells.
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Contributor(s) |
Hunt G, Boija A, Mannervik M |
Citation(s) |
36206738 |
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Submission date |
Jun 07, 2022 |
Last update date |
Oct 12, 2022 |
Contact name |
Mattias Mannervik |
E-mail(s) |
mattias.mannervik@su.se
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Organization name |
Stockholm University
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Department |
Dept. of Molecular Biosciences
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Street address |
Svante Arrhenius väg 20C
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City |
Stockholm |
ZIP/Postal code |
106 91 |
Country |
Sweden |
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Platforms (1) |
GPL30203 |
NextSeq 2000 (Drosophila melanogaster) |
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Samples (12)
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This SubSeries is part of SuperSeries: |
GSE186723 |
p300/CBP sustains Polycomb silencing by non-enzymatic functions |
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Relations |
BioProject |
PRJNA846733 |