Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release
Open accessAbstract
The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, 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 (minutes) 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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P300/CBP-induced acetylation has been implicated in the release of paused RNA polymerase at both enhancers and promoters to promote active transcription.
“This P300/CBP-induced acetylation has recently been implicated in the release of “paused” RNAP at both enhancers and promoters to promote active transcription [63].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [63]
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- Authors
- Narita, T., Ito, S., Higashijima, Y., Chu, W. K., Neumann, K., Walter, J., Satpathy, S., Liebner, T., Hamilton, W. B., Maskey, E., Prus, G., Shibata, M., Iesmantavicius, V., Brickman, J. M., Anastassiadis, K., Koseki, H., & Choudhary, C.
- Affiliations
- University of Copenhagen (DK)
- RIKEN Center for Integrative Medical Sciences (JP)
- Biotechnologisches Zentrum (DE)
- Chiba University (JP)
- Corresponding author
- Choudhary, Chunaram
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 81
- Issue
- 10
- Pages
- 2166-2182.e6
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W3136200267
- Cited by
- 228
- References
- 9
- Citations by year
- 2026: 38 · 2025: 60 · 2024: 53 · 2023: 35 · 2022: 31 · 2021: 11
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Novo Nordisk Fonden (NNF14OC0008541, NNF14CC0001, NNF17CC0027852)
- European Commission (SyBoSS FP7-242129)
- Core Research for Evolutional Science and Technology (13417643, JP19H05745)
- Japan Society for the Promotion of Science
- Danmarks Grundforskningsfond (DNRF116)
- Japan Agency for Medical Research and Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- CBP/p300, enhancer activation, super-enhancers, histone acetylation, deacetylase activity, RNA polymerase II recruitment, transcription initiation, pause release, TFIID, cell identity, transcriptional kinetics
- MeSH terms
- Bromodomain Containing Proteins, p300-CBP-Associated Factor, Acetylation, Animals, Chromatin, Enhancer Elements, Genetic, Histone Deacetylases, Histones, Lysine, Models, Biological, Nuclear Proteins, Protein Binding, RNA Polymerase II, Transcription Factors, Down-Regulation, Transcription Factor TFIID, p300-CBP Transcription Factors, Mice, Biocatalysis, Transcription Initiation, Genetic
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