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Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications
Author(s) -
Simithy Johayra,
Sidoli Simone,
Garcia Benjamin A.
Publication year - 2018
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201700309
Subject(s) - chromatin , histone , epigenetics , acetylation , epigenomics , histone code , chromatin remodeling , biology , histone h2a , histone methyltransferase , computational biology , microbiology and biotechnology , histone modifying enzymes , proteomics , chemistry , biochemistry , dna , dna methylation , nucleosome , gene expression , gene
Abstract The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers “flag” chromatin regions by catalyzing/removing covalent histone post‐translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout. The precursors of protein PTMs are mostly small metabolites. For instance, acetyl‐CoA is used for acetylation, ATP for phosphorylation, and S‐adenosylmethionine for methylation. Interestingly, PTMs such as acetylation can occur at neutral pH also without their respective enzyme when the precursor is sufficiently concentrated. Therefore, it is essential to differentially quantify the contribution of histone writers/erasers versus the effect of local concentration of metabolites to understand the primary regulation of histone PTM abundance. Aberrant phenotypes such as cancer cells have misregulated metabolism and thus the composition and the modulation of chromatin is not only driven by enzymatic tuning. In this review, the latest advances in mass spectrometry (MS) to analyze histone PTMs and the most adopted quantification methods for related metabolites, both necessary to understand PTM relative changes, are discussed.