Vestiges of a DNA methylation system in Drosophila melanogaster?

Abstract

The insect Drosophila melanogaster belongs to an atypical group of animals with no detectable genomic 5-methylcytosine^1,2,3. We found, unexpectedly, that the Drosophila genome potentially encodes two proteins that resemble a cytosine DNA methyltransferase and a mammalian methyl-CpG-binding-domain (MBD) protein, respectively. The hypothetical DNA methyltransferase, dDNMT, is closely related to the pmt1/DNMT2 family identified in fission yeast⁴ and mouse^5,6 (Fig. 1a). Attempts to transfer methyl groups from S-adenosylmethionine to DNA have not been successful using native members of this family, and bacterially expressed dDNMT was catalytically inactive in vitro (data not shown). Although the dDNMT transcript is present in embryonic, larval and adult flies (data not shown), the functional significance of the protein is unknown. Our report focuses on the Drosophila protein dMBD2/3, which is related to MBD2 and MBD3 of mammals⁷ (Fig. 1b). We detected two transcripts encoding dMBD2/3 in Drosophila cultured-cell RNA, 0-hour to 4-hour embryonic stages and adults, suggesting widespread expression of the gene (data not shown). The shorter splice variant lacks part of the methyl-CpG-binding-domain homology (dMBD2/3Δ; Fig. 2f; ref. 8, and data not shown).