RNA Binding to CBP Stimulates Histone Acetylation and Transcription

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

Research output: Contribution to journalArticle

101 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)135-149.e22
JournalCell
Volume168
Issue number1-2
DOIs
StatePublished - Jan 12 2017

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Bose, D. A., Donahue, G., Reinberg, D., Shiekhattar, R., Bonasio, R., & Berger, S. L. (2017). RNA Binding to CBP Stimulates Histone Acetylation and Transcription. Cell, 168(1-2), 135-149.e22. https://doi.org/10.1016/j.cell.2016.12.020