Methylation: lost in hydroxylation?

EMBO Rep. 2005 Apr;6(4):315-20. doi: 10.1038/sj.embor.7400379.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chromatin / metabolism*
  • DNA-Binding Proteins / metabolism
  • Histones / metabolism*
  • Hypoxia-Inducible Factor 1
  • Methylation
  • Mixed Function Oxygenases / metabolism
  • Models, Molecular*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Alignment
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Hypoxia-Inducible Factor 1
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • epe1 protein, S pombe
  • Mixed Function Oxygenases