Epigenetic control of retrotransposon silencing in somatic cells of Drosohpila by the cytosine 5 Methyltransferase DNMT2

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The central aim of our studies consists in resolving the epigenetic function of DNMT2 in the Drosophila model system. DNMT2 is involved in retrotransposon and repeatdependent gene silencing monitored by variegated expression of the white reporter gene. Histone methyltransferases involved in these silencing processes are SUV4-20 and SETDB1 and functional interdependence of DNMT2 with these enzymes in recognition, binding and epigenetic indexing at specific target site will be studied. First Dnmt2 point mutations were isolated and systematic genetic dissection of DNMT2 function in these processes will be performed. Dnmt2 is very early zygotically expressed and its epigenetic indexing in early embryogenesis is studied by ChIP analysis. Dnmt2 expression levels strongly depend on the genetic background. For identification of factors controlling Dnmt2 expression wild type populations will be assayed using transgenic expression reporter systems for genetic analysis. Beside analysis of the role of retrotransposons in control of DNMT2 dependent silencing processes the epigenetic function of a series of newly identified modifiers of these processes will be molecularly analysed. It will be studied whether a putative TET1 homolog of Drosophila functions in demethylation of 5-mC.