Functional characterization of DNA methylation in Drosophila

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DNA methylation plays an important role in epigenetic gene regulation of higher eukaryotes like plants and mammals. Loss (or reduction) of methylation in these organisms results in dramatic but little understood developmental problems. We have shown recently that genomic DNA of the fruit fly Drosophila melanogaster is methylated specifically during early embryogenesis. The genome sequence of Drosophila contains a single candidate gene, dDnmt2, that has been predicted to encode a (cytosine-5) DNA methyltransferase. Dnmt2 genes are the most widely distributed eukaryotic DNA methyltransferase genes suggesting an important function in epigenetic gene regulation. For a detailed characterization of dDnmt2 we will thoroughly analyze the functional organization of the gene and then generate transgenic flies that carry either a targeted deletion of the gene or a transgene for inducible overexpression. A detailed molecular analysis of mutant flies will provide important results regading the role of dDnmt2 as well as the function of DNA methylation during Drosophila development. These experiments will be complemented by an analysis of subnuclear dDnmt2 distribution and genomic 5-methylcytosine during fly development. The experimental accessibility of the fly will generate a large wealth of data that will significantly deepen our understanding of epigenetic inheritance and establish Drosophila as a central model system for DNA methylation research.