Figure 6: Overall model.
From: Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2
The basal activity of PRC2 towards H3K27 (left) is activated by the binding of a ‘repressive peptide’ to EED (middle), mediated by stabilization of SRM and thus the SET-I. The figure indicates that in the absence of these interactions, the SET-I has more thermal mobility. The propagation of repressive chromatin is mediated by activation through EED. When oncogenic histone mutant (H3K27M) binds to the SET active site (right), the additional contribution to avidity and absence of turnover leads to ‘stalling’ of PRC2, preventing propagation of the H3K27me3 mark. In addition to the H3 tail interactions with the minimal complex discussed above, the extended PRC2 complex (orange shape) makes extensive ncRNA38, and protein and DNA interactions with the nucleosome (grey shape).
