Cited by 447Genomics and Chromatin DynamicsCancer-related molecular mechanisms researchChromatin Remodeling and Cancer

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RNA Binding to CBP Stimulates Histone Acetylation and Transcription

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Bose, Daniel A., Donahue, Greg, Reinberg, Danny, Shiekhattar, Ramin, Bonasio, Roberto, Berger, Shelley L.·2017·Cell

DOI 10.1016/j.cell.2016.12.020PMC PMC5325706

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Abstract

CBP/p300 are transcription co-activators whose binding is a signature of enhancers, cis-regulatory elements that control patterns of gene expression in multicellular organisms. Active enhancers produce bi-directional enhancer RNAs (eRNAs) and display CBP/p300-dependent histone acetylation. Here, we demonstrate that CBP binds directly to RNAs in vivo and in vitro. RNAs bound to CBP in vivo include a large number of eRNAs. Using steady-state histone acetyltransferase (HAT) assays, we show that an RNA binding region in the HAT domain of CBP-a regulatory motif unique to CBP/p300-allows RNA to stimulate CBP's HAT activity. At enhancers where CBP interacts with eRNAs, stimulation manifests in RNA-dependent changes in the histone acetylation mediated by CBP, such as H3K27ac, and by corresponding changes in gene expression. By interacting directly with CBP, eRNAs contribute to the unique chromatin structure at active enhancers, which, in turn, is required for regulation of target genes.

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Authors: Bose, D. A., Donahue, G., Reinberg, D., Shiekhattar, R., Bonasio, R., & Berger, S. L.
Affiliations: University of Pennsylvania (US)
New York University (US)
University of Miami (US)
Corresponding author: Berger, Shelley L.
ORCID: Bose, Daniel A.
Donahue, Greg
Reinberg, Danny
Shiekhattar, Ramin
Bonasio, Roberto
Berger, Shelley L.
Venue: Cell
Publisher: Elsevier BV
Published: 2017-01
Volume: 168
Issue: 1-2
Pages: 135-149.e22
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2016.12.020
PMC: PMC5325706
OpenAlex: W2578822114
Cited by: 426
References: 79
Citations by year: 2026: 25 · 2025: 32 · 2024: 55 · 2023: 38 · 2022: 51 · 2021: 66 · 2020: 57 · 2019: 37 · 2018: 42 · 2017: 22
FWCI: 17.88
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: NIH (R01 CA078831)
NIH Innovator Award (DP2MH107055)
Searle Scholars Program (15-SSP-102)
March of Dimes Foundation (1-FY-15-344)
W.W. Smith Charitable Trust (C1404)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: CBP, P300, RNA binding, enhancer RNA, histone acetylation, histone acetyltransferase activity, H3K27ac, transcriptional coactivator, gene expression regulation
MeSH terms: Acetylation, Animals, Cell Line, Enhancer Elements, Genetic, Fibroblasts, Histones, RNA, Untranslated, p300-CBP Transcription Factors, Mice, Histone Acetyltransferases

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RNA Binding to CBP Stimulates Histone Acetylation and Transcription

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