Study of the functional role of DNA (cytosine-5)-methyltransferase superfamily genes, dDnmt2, in Drosophila melanogaster

Methylation of DNA at the C5 position of cytosine residues is found from prokaryote to eukaryote. DNA methylation at the mammalian genomes participates in the control of several interlinked biological processes, e.g., gene expression, cell growth, genomic imprinting, X-chromosome inactivation, and embryogenesis, which in turn are mediated through chromatin remodeling. The mammalian DNA methyltransferases (Dnmt), including Dnmt1, Dnmt2, Dnmt3A, and Dnmt3B, are a family of proteins with highly conserved motifs in their carboxyl terminal regions. Of these, Dnmt1 is the maintenance enzyme. Dnmt3A and Dnmt3B carry out the de novo methylation reaction. Unlike the above three enzymes, Dnmt2 lacks the N-terminal regulatory region.
Although recent studies have demonstrated residual DNA methylation activities of the mammalian Dnmt2 proteins and the Drosophila ortholog dDnmt2, the latter of which is the single DNA methyltransferase responsible for genome methylation of the fruit flies, the functional role of the Dnmt2 proteins remained unclear. We present evidence that intactness of the gene is required for maintenance of the normal lifespan of the fruit flies. In contrast, overexpression of dDnmt2 could extend Drosophila lifespan. The study links the Drosophila DNA methylation program with the longevity/aging, and has interesting implication on the eukaryotic DNA methylation programs in general.
A dDnmt2 deletion mutant was obtained from P element excision. The mutant arrested at third-instar larvae stage and cannot develop to pupa stage. RT-PCR data shown the temporal profiles of nuclear receptor gene are abnormal. Suggest that dDnmt2 may contribute to the Drosophila metamorphosis and ecdysone-signaling pathway.