Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Stephane Ronsseray¹, Augustin de Vanssay¹, Catherine Hermant¹, Antoine Boivin¹, Laure Teysset¹, Valérie Delmarre¹, Anne-Laure Bougé², Christophe Antoniewski^2,1. 1) Biol du Developpement, CNRS/UMR7622, Paris, France; 2) Drosophila Genetics and Epigenetics, CNRS/URA2578, Institut Pasteur, Paris, France.

   A paramutation is an interaction between two alleles of a locus, through which one allele induces a heritable modification of the other allele without modifying the DNA sequence. The paramutated allele retains the epigenetically-acquired properties in the succeeding generations and becomes itself paramutagenic. Although well characterized in plants, stably-inherited paramutations had not, until now, been described in animals. Using Trans-Silencing Effect (TSE), a homology-dependent repression mechanism discovered in the course of study of P transposable element repression, we have shown the existence of a fully penetrant and stable (>50 generations) paramutation in Drosophila melanogaster. In TSE, a P-transgene inserted in heterochromatin has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. Phenotypic and genetic analysis have shown that TSE exhibits variegation in ovaries, displays a maternal effect as well as epigenetic transmission through meiosis. We show that clusters of P-element derived transgenes exhibiting a strong capacity to induce TSE can convert other homologous transgene clusters stably incapable of TSE into strong silencers. This conversion is mediated by maternal inheritance of cytoplasm carrying piRNAs homologous to the transgenes. The paramutated cluster, previously unable to produce piRNAs, is converted into a piRNA-producing locus and is itself fully paramutagenic. TSE in Drosophila shows that paramutation can occur without pairing of the paramutagenic and the paramutated loci. Our work provides a model to analyze the emergence of piRNA loci, as well as trans-generational epigenetic effects observed in transposable element repression. Using a candidate gene approach, we investigate factors affecting paramutation in Drosophila.