Cell Reports
Volume 24, Issue 7, 14 August 2018, Pages 1722-1729
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2018.07.041Get rights and content
Under a Creative Commons license
open access

Highlights

  • CBP/P300 bromodomain inhibitor GNE-049 selectively blocks H3K27Ac at enhancers

  • H3K27Ac is required for enhancer function

  • GNE-049 blocks eRNA production and expression of enhancer-proximal genes

  • H3K27Ac at enhancers is required for growth of hematological cancers

Summary

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

enhancer
P300
CBP
bromodomain
histone acetylation
H3K27Ac

Cited by (0)

10

Lead Contact