title: Methylation: lost in hydroxylation?
abstract: Methylation of histone tails is a key determinant in forming active and silent states of chromatin. Histone methylation was regarded as irreversible until the recent identification of a lysine-specific histone demethylase (LSD1), which acts specifically on mono- and dimethylated histone H3 lysine 4. Here, we propose that the fission yeast protein Epe1 is a putative histone demethylase that could act by oxidative demethylation. Epe1 modulates the stability of silent chromatin and contains a JmjC domain. The Epe1 protein can be modelled onto the structure of the 2-oxoglutarate-Fe(II)-dependent dioxygenase, factor inhibiting hypoxia inducible factor (FIH), which is a protein hydroxylase that also contains a JmjC domain. Thus, Epe1 and certain other chromatin-associated JmjC-domain proteins may be protein hydroxylases that catalyse a novel histone modification. Another intriguing possibility is that, by hydroxylating the methyl groups, Epe1 and certain other JmjC-domain proteins may be able to demethylate mono-, di- or trimethylated histones.
authors.affiliation: Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh EH9 3JR, UK.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Trewick
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
mesh_terms: D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D008745:Methylation; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D051793:Hypoxia-Inducible Factor 1; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C475031:epe1 protein, S pombe; D006899:Mixed Function Oxygenases