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Protein arginine deiminase 4 antagonizes methylglyoxal-induced histone glycation.

Nature communications (2020-06-28)
Qingfei Zheng, Adewola Osunsade, Yael David
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PRMT1 Active human, recombinant, expressed in baculovirus infected insect cells, ≥70% (SDS-PAGE)
Sigma-Aldrich
GSK484, ≥98% (HPLC)
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
Water-18O, (for PET), 97 atom % 18O