A genetic screen for new Polycomb group genes in Drosophila melanogaster and biochemical purification of novel PcG protein complexes

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Repression of Drosophila homeotic genes by Polycomb group proteins presents a paradigm for heritable gene silencing during development. In the early Drosophila embryo, localized repressors determine in which segments homeotic genes must remain inactive. During subsequent development, homeotic genes stay heritably silenced in the cells derived from these segments even though the early repressors are no longer present. This heritable silencing requires the proteins of the Polycomb group. Several Polycomb group genes have been identified in Drosophila but no systematic screens for Polycomb group mutants have been performed. Notably, it appears that several Polycomb group genes with important roles in the silencing process have not been discovered yet. Here, I propose to use a genetic screen to identify novel Polycomb group genes in Drosophila. In brief, we will perform a saturation mutagenesis to screen for new mutants with Polycomb-like phenotypes in clones in the adult epidermis. The long-term aim will be to map and clone these new Polycomb group genes. Polycomb group proteins are conserved in both structure and function in vertebrates and several Polycomb group proteins function as repressors in plant development. It is therefore likely that the identification of new Polycomb group genes in Drosophila will have impacts for understanding epigenetic silencing processes in other organisms.