2. Academic Validation
  3. Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation

Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation

  • Cell Rep. 2018 Aug 14;24(7):1722-1729. doi: 10.1016/j.celrep.2018.07.041.
Ryan Raisner 1,  Samir Kharbanda 2,  Lingyan Jin 1,  Edwin Jeng 3,  Emily Chan 4,  Mark Merchant 4,  Peter M Haverty 5,  Russell Bainer 5,  Tommy Cheung 6,  David Arnott 6,  E Megan Flynn 7,  F Anthony Romero 8,  Steven Magnuson 9,  Karen E Gascoigne 10
Affiliations

Affiliations

  • 1 Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 2 Calico Labs, South San Francisco, CA 94080, USA.
  • 3 Program in Cancer Biology and Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • 4 Department of Translational Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 5 Department of Bioinformatics, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 6 Department of Protein Science, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 7 Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 8 Unity Biotechnology, Brisbane, CA 94005, USA.
  • 9 Department of Discovery Chemistry, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 10 Department of Discovery Oncology, Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: [email protected].
PMID: 30110629 DOI: 10.1016/j.celrep.2018.07.041
Abstract

Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer activity. However, the functional impact of this modification at enhancers is poorly understood. Here, we use a chemical genetics approach to acutely block the function of the cAMP response element binding protein (CREB) binding protein (CBP)/P300 bromodomain in models of hematological malignancies and describe a consequent loss of H3K27Ac specifically from enhancers, despite the continued presence of CBP/P300 at chromatin. Using this approach to dissect the role of H3K27Ac at enhancers, we identify a critical role for this modification in the production of enhancer RNAs and transcription of enhancer-regulated gene networks.

Keywords

CBP; H3K27Ac; P300; bromodomain; enhancer; histone acetylation.

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