Homeotic gene silencing in Drosophila.

Homeotic genes specify segment identity in Drosophila. Their pattern of expression is set early in the embryo by the transient expression of the segmentation genes. Later in development, when the products of the segmentation genes are no longer present, the Polycomb Group of genes (PcG) silences the homeotic genes within the appropriate segments. In an effort to study how PcG genes mediate silencing of homeotic genes, I carried out a screen for genetic interactions between a mutation in the Polycomb locus (Pc 3 ) and a series of mutations in genes that affect heterochromatic Position effect variegation (PEV). The idea that PcG silencing shares molecular mechanisms with PEV has existed for a long time, but no one has reported a detailed study in the literature. We observed that several PEV modifiers interacted strongly with Pc 3 . One such gene is Su(var)2-10, also called dPIAS. We set out to characterize Su(var)2-10 genetically, biochemically and in vivo in an effort to understand how it might control PcG silencing. The Su(var)2-10 gene product, bears a high sequence identity to mammalian PIAS proteins, some of which have been reported to function as E3 enzymes in a protein modification pathway called SUMOylation. Thus we assessed whether SUMOylation contributes to PcG silencing and to PEV, and whether the SU(VAR)2-10 protein is a SUMO E3 enzyme. In our effort to study interacting partners of SU(VAR)2-10, we identified the GAGA factor. We established that GAGA factor is a substrate for SUMOylation and that this modification has biological significance for GAGA function in PEV.