Enhancer Activity Requires CBP/P300 Bromodomain Dependent Histone H3K27 Acetylation

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 theCBP/P300 bromodomain in models of hematological malignancies, and describe aconsequent loss of H3K27Ac specifically from enhancers, despite the continuedpresence of CBP/P300 at chromatin. Using this approach to dissect the role ofH3K27Ac at enhancers, we identify a critical role for this modification in the productionof enhancer RNAs, and transcription of enhancer-regulated gene networks.