The role of acetylation of histone H3 lysine 27 in enhancer function

Abstract

The histone modification H3K27ac is a hallmark of active enhancers. However, its role in enhance-specific activity remains obscure. We applied mass spectrometry-based quantitative interaction proteomics to determine proteins that specifically bind H3K27ac. We identified GBAF, a non-canonical GLTSCR1L- and BRD9-containing SWI/SNF chromatin remodeling complex. GBAF was further systematically characterized in terms of protein composition and chromatin localization. A series of ChIP-seq experiments validated the interaction between GLTSCR1L and H3K27ac to be BRD9-dependent. Impairment of the H3K27ac recognition function of GBAF resulted in the dislocation of GLTSCR1L from its preferred binding sites and the genome-wide downregulation, specifically, of enhancer RNA transcription. We show that GBAF binds H3K27ac, and is an enhancer-specific chromatin remodeler involved in the transcriptional and regulatory activity of enhancers.