Role of PRC2-associated factors in stem cells and disease

The Polycomb group (PcG) of proteins form chromatin-binding complexes with histone-modifying activity. The two main PcG repressive complexes studied (PRC1 and PRC2) are generally associated with chromatin in its repressed state. PRC2 is responsible for methylation of histone H3 at lysine 27 (H3K27me3), an epigenetic mark that is linked with numerous biological processes, including development, adult homeostasis and cancer. The core canonical complex PRC2, which contains the EZH1/2, SUZ12 and EED proteins, may be extended and functionally manipulated through interactions with several other proteins. In this review, we focus on these PRC2-associated proteins. As PRC2 functions are diverse, the variability conferred by these sub-stoichiometrically associated members may help to understand specific changes in PRC2 activity, chromatin recruitment and distribution required for gene repression. It is well known that the Polycomb repressive complex 2 (PRC2) exerts gene repressive functions that are crucial during development and adult homeostasis. Therefore, it should be finely controlled and its deregulation could lead to disease states. Here, we review several factors that have been found associated with PRC2 and control its activity or its specific genomic targeting.