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Cell. 2017 Jan 12;168(1-2):135-149.e22. doi: 10.1016/j.cell.2016.12.020. Epub 2017 Jan 12.

RNA Binding to CBP Stimulates Histone Acetylation and Transcription.

Author information

1
Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Molecular Pharmacology and Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
3
Sylvester Comprehensive Cancer Center, Department of Human Genetics, University of Miami Miller School of Medicine, Biomedical Research Building, Room 719, 1501 NW 10th Avenue, Miami, FL 33136, USA.
4
Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Epigenetics Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bergers@upenn.edu.

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.

KEYWORDS:

CBP/p300; RNA-binding; acetyltransferase; chromatin modification; eRNA; enhancers; epigenetic enzymes; gene regulation; histone acetylation; non-coding RNA

PMID:
28086087
PMCID:
PMC5325706
DOI:
10.1016/j.cell.2016.12.020
[Indexed for MEDLINE]
Free PMC Article

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