Comprehensive mass spectrometry screening-derived atlas of HDAC inhibitors reveals histone-specific acetylation changes

Histone deacetylase inhibitors (HDACis) have emerged as valuable therapeutics for Cancer and Other diseases; however, their effects on histone post-translational modification remain poorly characterized. Here, we applied quantitative mass spectrometry and high-throughput Sequencing to systematically profile site-specific changes in histone modifications in response to a panel of HDACis. This platform enabled mapping of histone modification changes across hundreds of sites, including low-abundance histone marks. Furthermore, an integrative analysis of chromatin immunoprecipitation followed by Sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) data identified genome-wide binding sites for the low-abundance histone modification of H2A.Z acetylation in HeLa and MDA-MB-231 breast Cancer cells, highlighting the role of H2A.Z acetylation in regulating gene expression across diverse biological pathways, including specific genes involved in tumor suppressor pathways. Our findings provide a functional resource for identifying and quantifying histone modification changes and transcriptional regulation of histone H2A.Z acetylation following pharmacological perturbation.

CP: genomics; ChIP-seq; Entinostat; RNA-seq; breast cancer; histone H2A.Z acetylation; histone deacetylase inhibitors; mass spectrometry; post-translational modification.