Removing Epigenetic Marks

Science's STKE  12 Oct 2004:
Vol. 2004, Issue 254, pp. tw368
DOI: 10.1126/stke.2542004tw368

Enzymes that covalently modify histones generally come in pairs that have opposing effects on gene expression, such as acetylases and deacetylases or kinases and phosphatases. Notable exceptions are the enzymes that methylate histones on lysine or arginine residues. No enzymes had been identified that remove these potent and very stable epigenetic marks, until now. Wang et al. show that the enzyme peptidylarginine deiminase 4 (PAD4), which converts unmodified arginine residues to citrulline in histones, can also convert methylated arginine residues in histones to citrulline, thereby removing the methyl mark ("demethylimination"). PAD4 can modulate the expression of genes known to be regulated by arginine histone methylases, which suggests that at least one of the elusive histone demethylases may have been identified.

Y. Wang, J. Wysocka, J. Sayegh, Y.-H. Lee, J. R. Perlin, L. Leonelli, L. S. Sonbuchner, C. H. McDonald, R. G. Cook, Y. Dou, R. G. Roeder, S. Clarke, M. R. Stallcup, C. D. Allis, S. A. Coonrod, Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306, 279-283 (2004). [Abstract] [Full Text]