Drosophila proteins related to vertebrate DNA (5-cytosine) methyltransferases

DNA methylation at CpG residues is closely associated with a number of biol ogical processes during vertebrate development. Unlike the vertebrates, how ever, several invertebrate species, including the Drosophila, do not have a pparent DNA methylation in their genomes. Nor have there been reports on a DNA (5-cytosine) methyltransferase (CpG MTase) found in these invertebrates . We now present evidence for two CpG MTase-like proteins expressed in Dros ophila cells. One of these, DmMTR1, is a protein containing peptide epitope s immunologically related to the conserved motifs I and IV in the catalytic domain of the mammalian dnmt1. DmMTR1 has an apparent molecular mass of 22 0 kDa and, similar to mammalian dnmt1, it also interacts in vivo with the p roliferating cell nuclear antigen. During interphase of the syncytial Droso phila embryos, the DmMTR1 molecules are located outside the nuclei, as is d nmt1 in the mouse blastocyst. However, DmMTR1 appears to be rapidly transpo rted into, and then out of the nuclei again, as the embryos undergo mitotic waves. Immunofluorescent data indicate that DmMTR1 molecules "paint" the w hole set of condensed Drosophila chromosomes throughout the mitotic phase, suggesting they may play an essential function in the cell-cycle regulated condensation of the Drosophila chromosomes. Through search in the genomic d atabase, we also have identified a Drosophila polypeptide, DmMT2, that exhi bits high sequence homology to the mammalian dnmt2 and the yeast CpG MTase homolog pmt1. The expression of DmMT2 appears to be developmentally regulat ed. We discuss the evolutionary and functional implications of the discover y of these two Drosophila proteins related to mammalian CpG MTases.