Protein arginine deiminase 4 antagonizes methylglyoxal-induced histone glycation Journal Article


Authors: Zheng, Q.; Osunsade, A.; David, Y.
Article Title: Protein arginine deiminase 4 antagonizes methylglyoxal-induced histone glycation
Abstract: Protein arginine deiminase 4 (PAD4) facilitates the post-translational citrullination of the core histones H3 and H4. While the precise epigenetic function of this modification has not been resolved, it has been shown to associate with general chromatin decompaction and compete with arginine methylation. Recently, we found that histones are subjected to methylglyoxal (MGO)-induced glycation on nucleophilic side chains, particularly arginines, under metabolic stress conditions. These non-enzymatic adducts change chromatin architecture and the epigenetic landscape by competing with enzymatic modifications, as well as changing the overall biophysical properties of the fiber. Here, we report that PAD4 antagonizes histone MGO-glycation by protecting the reactive arginine sites, as well as by converting already-glycated arginine residues into citrulline. Moreover, we show that similar to the deglycase DJ-1, PAD4 is overexpressed and histone citrullination is upregulated in breast cancer tumors, suggesting an additional mechanistic link to PAD4’s oncogenic properties. © 2020, The Author(s).
Keywords: controlled study; protein expression; nonhuman; mouse; animal tissue; cell viability; gene; breast cancer; gene expression; animal experiment; animal model; protein; in vitro study; enzyme activity; amino acid sequence; epigenetics; histone; chromatin; histone h3; cancer cell; cell fractionation; arginine; protein methylation; enzyme; nucleosome; nucleophilicity; protein glycosylation; precipitation; citrulline; metabolic stress; cancer; article; methylglyoxal; mcf-7 cell line; hek293t cell line; protein arginine deiminase type 4; citrullination
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-06-26
Start Page: 3241
Language: English
DOI: 10.1038/s41467-020-17066-y
PUBMED: 32591537
PROVIDER: scopus
PMCID: PMC7319962
DOI/URL:
Notes: Article -- Export Date: 3 August 2020 -- Source: Scopus
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  1. Qingfei Zheng
    8 Zheng