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

  • Cell Rep. 2026 May 26;45(5):117289. doi: 10.1016/j.celrep.2026.117289.
Rashmi Karki  1 ,  Francisca N De Luna Vitorino  1 ,  Richard M Searfoss  1 ,  Joanna K Lempiäinen  1 ,  Cheryl H Arrowsmith  2 ,  Benjamin A Garcia  3
Affiliations
  • 1. Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA.
  • 2. Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada; Princess Margaret Center, Toronto, ON, Canada.
  • 3. Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: [email protected].
PMID: 42030158 DOI: 10.1016/j.celrep.2026.117289
Abstract

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.

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