Reversible histone glycation is associated with disease-related changes in chromatin architecture Journal Article

Authors: Zheng, Q.; Omans, N. D.; Leicher, R.; Osunsade, A.; Agustinus, A. S.; Finkin-Groner, E.; D'Ambrosio, H.; Liu, B.; Chandarlapaty, S.; Liu, S.; David, Y.
Article Title: Reversible histone glycation is associated with disease-related changes in chromatin architecture
Abstract: Cellular proteins continuously undergo non-enzymatic covalent modifications (NECMs) that accumulate under normal physiological conditions and are stimulated by changes in the cellular microenvironment. Glycation, the hallmark of diabetes, is a prevalent NECM associated with an array of pathologies. Histone proteins are particularly susceptible to NECMs due to their long half-lives and nucleophilic disordered tails that undergo extensive regulatory modifications; however, histone NECMs remain poorly understood. Here we perform a detailed analysis of histone glycation in vitro and in vivo and find it has global ramifications on histone enzymatic PTMs, the assembly and stability of nucleosomes, and chromatin architecture. Importantly, we identify a physiologic regulation mechanism, the enzyme DJ-1, which functions as a potent histone deglycase. Finally, we detect intense histone glycation and DJ-1 overexpression in breast cancer tumors. Collectively, our results suggest an additional mechanism for cellular metabolic damage through epigenetic perturbation, with implications in pathogenesis. © 2019, The Author(s).
Keywords: immunohistochemistry; controlled study; protein expression; protein phosphorylation; gene mutation; human cell; sequence analysis; genetics; nonhuman; protein analysis; animal cell; mouse; animal; metabolism; animals; mice; cell protein; protein; cancer cell culture; drug effect; pathology; cell line, tumor; breast neoplasms; physiology; chemistry; protein processing; protein processing, post-translational; genetic transfection; xenograft; protein purification; histone; chromatin; chromatin immunoprecipitation; epigenesis, genetic; breast tumor; bioassay; recombinant protein; tumor cell line; western blotting; glycosylation; cell fractionation; dna sequence; high performance liquid chromatography; genetic epigenesis; cell metabolism; histones; protein cross linking; chemical reaction; peptide synthesis; protein modification; acetylation; computer analysis; nucleosome; nucleosomes; pigment; cell; tumor microenvironment; advanced glycation end product; electrospray mass spectrometry; array; size exclusion chromatography; histone acetylation; humans; human; female; article; breast cancer cell line; heterografts; methylglyoxal; park7 protein, human; protein deglycase dj-1; deglycation assay; glycation; glycation assay; non enzymatic covalent modification; nucleosomal array; glycation end products, advanced; pyruvaldehyde
Journal Title: Nature Communications
Volume: 10
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2019-03-20
Start Page: 1289
Language: English
DOI: 10.1038/s41467-019-09192-z
PUBMED: 30894531
PROVIDER: scopus
PMCID: PMC6426841
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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