The mysterious presence of a 5-methylcytosine oxidase in the Drosophila genome: possible explanations

Cell Cycle. 2013 Nov 1;12(21):3357-65. doi: 10.4161/cc.26540. Epub 2013 Sep 19.


5-methylcytosine is an important epigenetic modification involved in gene control in vertebrates and many other complex living organisms. Its presence in Drosophila has been a matter of debate and recent bisulfite sequencing studies of early-stage fly embryos have concluded that the genome of Drosophila is essentially unmethylated. However, as we outline here, the Drosophila genome harbors a well-conserved homolog of the TET protein family. The mammalian orthologs TET1/2/3 are known to convert 5-methylcytosine into 5-hydroxymethylcytosine. We discuss several possible explanations for these seemingly contradictory findings. One possibility is that the 2 modified cytosine bases are generated in Drosophila only at certain developmental stages and in a cell type-specific manner during neurogenesis. Alternatively, Drosophila Tet and its mammalian homologs may carry out catalytic activity-independent functions, and the possibility that these proteins may oxidize 5-methylcytosine in RNA created by the methyltransferase Dnmt2 should also be strongly considered.

Keywords: 5-methylcytosine; DNA methylation; Drosophila; dioxygenase; epigenetics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 5-Methylcytosine / metabolism*
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • CpG Islands
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics*
  • Embryo, Nonmammalian
  • Epigenesis, Genetic
  • Genome, Insect*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mammals
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Processing, Post-Translational*
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Drosophila Proteins
  • Isoenzymes
  • 5-Methylcytosine
  • Mt2 protein, Drosophila
  • DNA (Cytosine-5-)-Methyltransferases