Human PAD4 Regulates Histone Arginine Methylation Levels via Demethylimination
| Autor: | Robert G. Roeder, Yali Dou, C. David Allis, Youngho Lee, Lakshmi S. Sonbuchner, Lauriebeth Leonelli, Steven Clarke, Joanna Wysocka, Michael R. Stallcup, Joyce Sayegh, Julie R. Perlin, Charles H. McDonald, Richard G. Cook, Scott A. Coonrod, Yanming Wang |
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| Rok vydání: | 2004 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Hydrolases Recombinant Fusion Proteins Blotting Western Molecular Sequence Data HL-60 Cells Arginine Methylation Histones Methylamines Protein-Arginine Deiminase Type 4 Genes Reporter Histone arginine methylation Cell Line Tumor Presenilin-2 Histone methylation Humans Histone code Amino Acid Sequence Promoter Regions Genetic Calcimycin Epigenomics Multidisciplinary Ionophores biology EZH2 Membrane Proteins Recombinant Proteins Histone citrullination Histone Gene Expression Regulation Biochemistry Histone methyltransferase Protein-Arginine Deiminases biology.protein Citrulline |
| Zdroj: | Science. 306:279-283 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | 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 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 histones. |
| Databáze: | OpenAIRE |
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