Human PAD4 regulates histone arginine methylation levels via demethylimination
Human PAD4 regulates histone arginine methylation levels via demethylimination
复制标题
DOI：
10.1126/science.1101400
复制
发表时间：
2004-10-08
期刊：
影响因子：
56.9
通讯作者：
Coonrod, SA
中科院分区：
文献类型：
--
作者：
Wang, Y;Wysocka, J;Coonrod, SA
历史上精氨酸（Arg）和赖氨酸残基的甲基化与基因调控的表观遗传形式相关。虽然组蛋白甲基转移酶是已知的，但使历史去甲基化的酶尚未被鉴定。在这里，我们证明了人肽基精氨酸脱亚胺酶4（PAD 4）通过将甲基精氨酸转化为瓜氨酸并释放甲胺来调节组蛋白精氨酸甲基化。PAD 4靶向组蛋白H3和H4中的多个位点，包括被辅激活剂CARM 1（H3 Arg（17））和PRMT 1（H4 Arg（3））甲基化的那些位点。组蛋白Arg甲基化的降低，伴随瓜氨酸的增加，需要人HL-60粒细胞中的PAD 4活性。此外，PAD 4活性与MCF-7细胞中雌激素反应基因的转录调节有关。这些数据表明，PAD 4介导的基因表达，通过调节精氨酸甲基化和瓜氨酸在历史上。
Methylation of arginine (Arg) and lysine residues in histories has been correlated with epigenetic forms of gene regulation. Although histone methyltransferases are known, enzymes that demethylate histories 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 Arg(17)) and PRMT1 (H4 Arg(3)). 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 histories.