Fig. 3.

Oncohistones and H3K27me3 antagonistically regulate PRC2 activity in cis. a Genome browser views of H3.3/oncohistone (green tracks, top panel) and H3K27me3 (blue tracks, bottom panel) occupancy in wild-type (light), H3.3K27M mutant (mut, medium), and H3-like K27M mutant (H3-like mut, dark) worms (100 kb windows). Genes and H3K27me3 domain annotations are highlighted at the bottom of the genome view. The domains are defined based on comparison of H3K27me3 occupancy between wild type: (i) autosomal signal is maintained, (ii) autosomal signal is lost, (iii) autosomal signal never present, (iv) chromosome X signal is maintained. b Boxplots showing H3K27me3 occupancy per chromosome in wild type (light blue), mut (medium blue), and H3-like mut (dark blue). c H3.3/oncohistone (green) and H3K27me3 (blue) occupancy in identified domains in wild type (light), mut (medium), and H3-like mut (dark). d Heat map showing hierarchical clustering of 10 kb bins covering the entire genome in mut (left panel) and H3-like mut (right panel) worms based on levels of H3K27me3 before and after acquiring oncohistone mutation, and oncohistone incorporation. Autosomes and X chromosome were clustered and are shown separately. e Model for oncohistone-mediated regulation of PRC2. PRC2 activity is locally both positively regulated by existing H3K27me3 and inhibited by incorporated oncohistones, and the in cis balance between these two factors determines the pattern of H3K27me3 in mutant cells