Fig. 7.

Model for local, concentration-dependent inhibition of PRC2 by H3.3K27M oncohistones. Incorporation of oncohistones locally disrupts the positive regulatory feedback loop between existing H3K27me3 and PRC2. Oncohistone presence in regions of low H3K27me3 results in a local reduction of H3K27me3 propagation by PRC2 and in a gradual loss of the mark. Free PRC2 can redistribute to regions with higher H3K27me3 occupancy, where it may result in local gains of the mark. In domains where levels of H3K7me3 are high, allosteric activation of PRC2 is sufficient to maintain the mark even in the presence of some oncohistone incorporation