Methylation: lost in hydroxylation?

Sarah C Trewick; Paul J McLaughlin; Robin C Allshire

doi:10.1038/sj.embor.7400379

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Methylation: lost in hydroxylation?

Sarah C Trewick·Paul J McLaughlin·Robin C Allshire

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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.

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Amino Acid Sequence Chromatin DNA-Binding Proteins Histones Hypoxia-Inducible Factor 1 Methylation Mixed Function Oxygenases Models, Molecular Molecular Sequence Data Nuclear Proteins Protein Structure, Tertiary Schizosaccharomyces Schizosaccharomyces pombe Proteins Sequence Alignment Transcription Factors Comparative Study Journal Article Research Support, Non-U.S. Gov't

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Sarah C Trewick, Paul J McLaughlin, Robin C Allshire. 2005. Methylation: lost in hydroxylation?. https://doi.org/10.1038/sj.embor.7400379

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