TRANSCRIPTIONAL REPRESSION BY DROSOPHILA AND MAMMALIAN POLYCOMB GROUPPROTEINS IN TRANSFECTED MAMMALIAN-CELLS

The Polycomb group (Pc-G) genes are essential for maintaining the prop er spatially restricted expression pattern of the homeotic loci during Drosophila development. The Pc-G proteins appear to function at targe t loci to maintain a state of transcriptional repression. The murine o ncogene bmi-1 has significant homology to the Pc-G gene Posterior sex combs (Psc) and a highly related gene, Suppressor two of zeste [Sn(z)2 ]. We show here that the proteins encoded by bmi-l and the Pc-G genes Polycomb (Pc) and Psc as well as Su(z)2 mediate repression in mammalia n cells when targeted to a promoter by LexA in a cotransfection system . These fusion proteins repress activator function by as much as 30-fo ld, and the effect on different activation domains is distinct for eac h Pc-G protein. Repression is observed when the LexA fusion proteins a re bound directly adjacent to activator binding sites and also when bo und 1,700 bases from the promoter. These data demonstrate that the pro ducts of the Pc-G genes can significantly repress activator function o n transiently introduced DNA. We suggest that this function contribute s to the stable repression of targeted loci during development.