Regulation of histone methylation by demethylimination and demethylation

Abstract

Modification of histone molecules within chromatin has a profound effect on genome structure and function. More specifically, methylation of histone arginine and lysine residues is involved in regulating transcription, epigenetic inheritance and controlling cell fate. Until recently, histone methylation was considered a stable modification. The identification of a histone deiminase and histone demethylases has demonstrated that histone methylation can be dynamically regulated. PADI4 can demethyliminate methylated arginine residues to produce citrulline. Although this reaction does not regenerate arginine, it reveals a mechanism by which arginine methylation can be antagonized. LSD1 uses an amine oxidase reaction to directly remove histone lysine mono- and di-methylation. Removal of H3K4 and H3K9 methylation by LSD1 contributes to transcriptional repression and activation, respectively. JmjC-domain-containing proteins encode a family of histone lysine demethylases that can remove all three methylation states. Members of this family have been shown to catalyse the removal of H3K4, H3K9 and H3K36 methylation. Additional uncharacterized demethylation reaction mechanisms are likely to exist given the extensive complement of methylated histone residues and modification states.