The Drosophila extra sex combs protein contains WD motifs essential for its function as a repressor of homeotic genes.

Extra sex combs is a member of the Polycomb Group genes, whose products are required for stable long term transcriptional repression of the homeotic genes of the Bithorax and Antennapedia complexes. The Pc-G proteins are required to maintain the spatially restricted domains of homeotic gene expression established by the transiently expressed repressors, e.g., hunchback, but are not required for the functioning of these early repressors. This implies two distinct modes of repression and raises the question: how does the transition from early transient repression to stable Pc-G-mediated repression occur? While other Pc-G proteins are required continuously throughout development, the esc RNA is only present transiently in early embryos, suggesting that esc may play a role in mediating this transition to stable long term Pc-G-mediated repression. The predicted esc protein contains multiple copies of the WD motif, found in G-protein beta subunits as well as non-G proteins involved in diverse cellular functions, including transcriptional repression. The sequence alterations of a number of esc mutations cause amino acid substitutions within the WD repeats, identifying them as essential for the function of the esc protein as a repressor of homeotic gene expression. Other WD proteins are components of reversible macromolecular assemblies and the WD motif has recently been directly implicated in mediating interactions with other proteins in such complexes. We propose that the esc protein is similarly involved in the initial recruitment of Pc-G repressors to the homeotic genes to establish their stable long term repression.