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Abstract

In the first part of my talk, I will present you work aimed at identifying the biological functions of the Drosophila DNA methyl transferase 2 (Dnmt2) gene. Then, I will present you current work on an example of paramutation in Drosophila.
The hereditary transmission of a phenotype independent from DNA sequence implies some epigenetic mechanism. Paramutation is an epigenetic phenomenon observed in plants and animals. To investigate paramutation in Drosophila, we used the P{ry[+t7.2]=PZ}Dl05151 P-element insertion in the Drosophila melanogaster genome that causes a dominant visible phenotype: the presence of characteristic extra-veins in the fly wings. The insert is a PZ element located 680 bp upstream of the Delta (Dl) gene, encoding the Notch ligand involved in wing development. The extra-vein phenotype presents variable expressivity and incomplete penetrance. In the F2 from a cross between the heterozygous transgenic stock and rosy506 flies, we observed the transmission of the extra-vein phenotype to wild-type flies without the transgene, independently of gender.
This experiment recalls the one previously carried out in mice where a white tail tip phenotype was observed in wild-type animals for the Kit locus, coming from heterozygous Kittm1Alf/Kit+ mice. This phenotype is efficiently transmitted and results from a decrease in c-Kit messenger RNA levels with the accumulation of non-polyadenylated RNA molecules. A heritable white tail tip phenotype is also observed after microinjection into fertilized eggs of either total RNA or fragments of c-Kit and cognate microRNAs. This is an example of paramutatiion, the heritable transmission of a phenotypic change not linked to a classical genetic modification. A ‘paramutable’ allele that has been combined in heterozygotes with a ‘paramutagenic’ form of the locus transmits the phenotype of the heterozygotes to the wild-type progeny. Distinct from silencing events so far described by Ronsseray et al., here we deal with a dominant effect with versatile and reversible signals.