Figure 8.

Spreading of PRC2 activity after initial recruitment. (A) PRC2 targets are engaged in a network of interactions wherein nucleation sites are concentrated, forming Polycomb foci. Following the nucleation event, PRC2 spreads H3K27me2/3 domains across the genome proximally as well as distally via long-range 3D contacts, all within Polycomb foci. (B) Detailed mechanism by which PRC2 spreads the products of its catalysis. PRC2 first catalyzes H3K27me2 at the nucleation sites (strong or weak), which are then converted to H3K27me3 once PRC2 reaches sufficient concentrations. Through binding to H3K27me3, PRC2 is allosterically stimulated and rapidly spreads H3K27me2 to adjacent chromatin. H3K27me2 is then converted to H3K27me3, and, as PRC2 moves further from the nucleation sites, its stability on chromatin decreases such that H3K27me3 domains remain proximal and H3K27me2 domains remain distal to its nucleation sites. The strong and weak nucleation sites engage in long-range interactions.