Human PAD4 regulates histone arginine methylation levels via demethylimination.

Article Details

Citation

Copy to clipboard

Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y, Roeder RG, Clarke S, Stallcup MR, Allis CD, Coonrod SA

Human PAD4 regulates histone arginine methylation levels via demethylimination.

Science. 2004 Oct 8;306(5694):279-83. Epub 2004 Sep 2.

PubMed ID

15345777 [ View in PubMed

]

Abstract

Methylation of arginine (Arg) and lysine residues in histones has been correlated with epigenetic forms of gene regulation. Although histone methyltransferases are known, enzymes that demethylate histones have not been identified. Here, we demonstrate that human peptidylarginine deiminase 4 (PAD4) regulates histone Arg methylation by converting methyl-Arg to citrulline and releasing methylamine. PAD4 targets multiple sites in histones H3 and H4, including those sites methylated by coactivators CARM1 (H3 Arg17) and PRMT1 (H4 Arg3). A decrease of histone Arg methylation, with a concomitant increase of citrullination, requires PAD4 activity in human HL-60 granulocytes. Moreover, PAD4 activity is linked with the transcriptional regulation of estrogen-responsive genes in MCF-7 cells. These data suggest that PAD4 mediates gene expression by regulating Arg methylation and citrullination in histones.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Citrulline	Protein-arginine deiminase type-4	Protein	Humans	Unknown	Not Available	Details

Polypeptides

Name	UniProt ID
Protein-arginine deiminase type-4	Q9UM07	Details