Abstract

As cells differentiate they acquire distinct gene expression profiles that cells “remember” when divide. Key to this memory are epigenetic mechanisms, which control gene expression in a heritable way that does not involve changes in the DNA sequence. Polycomb proteins comprise the most appreciated regulatory system of this kind. Polycomb proteins act in concert to repress multiple master regulatory genes and thereby prevent alternative gene expression programs from being executed within the same cell. Polycomb repression of the master regulatory genes is specific and robust. Paradoxically, although the Polycomb proteins are active in all cells, select target genes are spared from the repression in cells where they have to remain active. In addition to targeted repression, Polycomb proteins survey the entire genome in a hit-and-run fashion to suppress pervasive transcription. In this presentation I will focus on recent advances in our understanding of how the Polycomb proteins target specific genes in a way that “senses” their transcriptional status. I will present our view of the role of covalent histone modifications in the process and try to connect the “targeted” and “hit-and-run” modes of Polycomb regulation.