Mass spectrometry to study chromatin compaction

Stephanie Stransky, Jennifer Aguilan, Jake Lachowicz, Carlos Madrid-Aliste, Edward Nieves, Simone Sidoli

Research output: Contribution to journalReview articlepeer-review

Abstract

Chromatin accessibility is a major regulator of gene expression. Histone writers/erasers have a critical role in chromatin compaction, as they “flag” chromatin regions by catalyzing/removing covalent post-translational modifications on histone proteins. Anomalous chromatin decondensation is a common phenomenon in cells experiencing aging and viral infection. Moreover, about 50% of cancers have mutations in enzymes regulating chromatin state. Numerous genomics methods have evolved to characterize chromatin state, but the analysis of (in)accessible chromatin from the protein perspective is not yet in the spotlight. We present an overview of the most used approaches to generate data on chromatin accessibility and then focus on emerging methods that utilize mass spectrometry to quantify the accessibility of histones and the rest of the chromatin bound proteome. Mass spectrometry is currently the method of choice to quantify entire proteomes in an unbiased large-scale manner; accessibility on chromatin of proteins and protein modifications adds an extra quantitative layer to proteomics dataset that assist more informed data-driven hypotheses in chromatin biology. We speculate that this emerging new set of methods will enhance predictive strength on which proteins and histone modifications are critical in gene regulation, and which proteins occupy different chromatin states in health and disease.

Original languageEnglish (US)
Article number140
Pages (from-to)1-21
Number of pages21
JournalBiology
Volume9
Issue number6
DOIs
StatePublished - 2020

Keywords

  • Chromatin
  • DNA methylation
  • Histone
  • Mass spectrometry
  • Post-translational modification
  • Proteome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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