THE DROSOPHILA ESC AND E(Z) PROTEINS ARE DIRECT PARTNERS IN POLYCOMB GROUP-MEDIATED REPRESSION

The extra sex combs (esc) and Enhancer of zeste [E(z)] proteins are me mbers of the Drosophila Polycomb group (Pc-G) of transcriptional repre ssors. Here we present evidence for direct physical interaction betwee n the esc and E(z) proteins using yeast two-hybrid and in vitro bindin g assays. In addition, coimmunoprecipitation from embryo extracts demo nstrates association of esc and E(z) in vivo. We have delimited the es c-binding domain of E(z) to an N-terminal 33-amino-acid region. Furthe rmore, we demonstrate that site directed mutations in the esc protein previously shown to impair esc function in vivo disrupt esc-E(z) inter actions in vitro. We also show an in vitro interaction between the hee d and EZH1 proteins, which are human homologs of esc and E(z), respect ively. These results suggest that the esc-E(z) molecular partnership h as been conserved in evolution. Previous studies suggested that esc is primarily involved in the early stages of Pc-G-mediated silencing dur ing embryogenesis. However, E(z) is continuously required in order to maintain chromosome binding by other Pc-G proteins. In light of these earlier observations and the molecular data presented here, we discuss how esc-E(z) protein complexes may contribute to transcriptional sile ncing by the Pc-G.