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.


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.

MeSH terms

  • Acetylation
  • Binding Sites
  • Cell Line, Tumor
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Enhancer Elements, Genetic*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism
  • Protein Binding
  • Protein Domains
  • Protein Processing, Post-Translational*
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Transcription, Genetic
  • p300-CBP Transcription Factors / genetics*
  • p300-CBP Transcription Factors / metabolism


  • Chromatin
  • Histones
  • RNA, Neoplasm
  • p300-CBP Transcription Factors
  • Lysine