HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies.

ABSTRACT: Histone acetylation levels are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) that antagonistically control the overall balance of this post-translational modification. HDAC inhibitors (HDACi) are potent agents that disrupt this balance and are used clinically to treat diseases including cancer. Despite their use, little is known about their effects on chromatin regulators, particularly those that signal through lysine acetylation. We apply quantitative genomic and proteomic approaches to demonstrate that HDACi robustly increases a low-abundance histone 4 polyacetylation state, which serves as a preferred binding substrate for several bromodomain-containing proteins, including BRD4. Increased H4 polyacetylation occurs in transcribed genes and correlates wit

SUBMITTER: Slaughter MJ 

PROVIDER: S-EPMC7886050 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature