Comprehensive mass spectrometry screening-derived atlas of HDAC inhibitors reveals histone specific acetylation changes [ChIP-seq]

Histone deacetylases inhibitors (HDACi) have emerged as valuable therapeutics in cancer and other diseases, yet their effect on histone post-translational modification remains incompletely characterized. Here, we applied quantitative mass spectrometry and high throughput sequencing to systematically profile site-specific histone modification changes in response to a panel of HDAC inhibitors. This platform enabled mapping of histone modification changes across hundreds of sites including low abundant histone marks. Furthermore, integrative analysis of ChIP-seq and RNA-seq identified genome wide binding site for a low-abundant histone mark H2A.Z acetylation in HeLa cells and MDA-MB-231 breast cancer cells, highlighting the role of H2A.Z acetylation in regulating gene expression through various biological pathways and specific genes involved in tumor suppressor pathways. Our findings provide a functional resource for identification and quantification of epigenetic changes and transcriptional regulation of histone H2A.Z acetylation upon pharmacological perturbation