Language

English

Publication Date

1-1-2026

Journal

Mass Spectrometry Reviews

DOI

10.1002/mas.21941

PMID

40452177

PMCID

PMC12974565

PubMedCentral® Posted Date

6-1-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM analysis and highlight the advantages of mass spectrometry techniques in providing comprehensive and quantitative insights into histone proteoforms. Key considerations in experimental design, sample preparation, chromatographic separation, and data analysis are outlined for the effective application of mass spectrometry for histone proteoform studies. By integrating these technological advancements on the side of sample preparation, instrumentation, and data processing a deeper understanding of chromatin regulation through PTM crosstalk is achieved, paving the way for mass spectrometry-based proteomics to spearhead the discovery of novel therapeutic strategies with proteoform level specificity.

Keywords

Histones, Protein Processing, Post-Translational, Mass Spectrometry, Proteomics, Humans, Animals, Chromatin, Epigenesis, Genetic, Histone, Epigenetics, PTM crosstalk, Top-down Mass Spectrometry, Proteoform

Published Open-Access

yes

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