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Status |
Public on Mar 24, 2021 |
Title |
Enhancers are Activated by p300/CBP Activity-Dependent PIC Assembly, RNAPII Recruitment and Pause Release [ATAC-Seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The metazoan-specific acetyltransferase p300/CBP is involved in activating signalinduced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors, but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a ‘recruit-and-release’ mechanism to simultaneously promote RNAPII recruitment and pause release, and thereby, enables kinetic activation of enhancer-mediated transcription.
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Overall design |
Chromatin accessibility changes before and after A-485 treatment in mouse ES cell using ATAC-Seq.
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Contributor(s) |
Narita T, Hamilton WB, Choudhary C |
Citation(s) |
33765415 |
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Submission date |
Mar 03, 2020 |
Last update date |
Apr 01, 2021 |
Contact name |
Chunarum Choudhary |
E-mail(s) |
chuna.choudhary@cpr.ku.dk
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Organization name |
University of Copenhagen
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Department |
Novo Nordisk Foundation Center for Protein Research
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Lab |
Choudhary Group
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Street address |
Blegdamsvej 3B
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City |
Copenhagen N |
State/province |
--- Select a state --- |
ZIP/Postal code |
2200 |
Country |
Denmark |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE146328 |
Enhancers are Activated by p300/CBP Activity-Dependent PIC Assembly, RNAPII Recruitment and Pause Release |
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Relations |
BioProject |
PRJNA610086 |
SRA |
SRP251466 |