Polycomb group (PcG) proteins are major chromatin-bound factors that can read and modify chromatin states to maintain gene silencing throughout development. Here we focus on a close homolog of the PcG protein Posterior sex combs to better understand how these proteins affect regulation. This homolog, called Suppressor 2 of zeste [Su(z)2] is composed of two regions: the N-terminal homology region (HR), which serves as a hub for protein interactions, and the C-terminal region (CTR), which is believed to harbor the core activity of compacting chromatin. Here, we describe our classical genetic studies to dissect the structure of Su(z)2. Surprisingly, we found that the CTR is dispensable for viability. Furthermore, the core activity of Su(z)2 seems to reside in the HR instead of the CTR. Remarkably, our data also suggest a regulatory cascade between CTR and HR of Su(z)2, which, in turn, may help prioritize the myriad of PcG interactions that occur with the HR.
