Fig. 2

The H3K27M variant interferes with the EZH2 subunit within the PRC2 complex. A The EZH2 subunit within the PRC2 complex is involved in histone methylation and subsequent transcriptional repression. H3K27M variant proteins interfere with histone methylation through an inhibitory interaction with the EZH2 subunit, while wild-type proteins do not. B In the H3K27 wild type, trimethylation of lysine residues preserves transcriptional repression. In the H3K27M variant, methylation is reduced, resulting in chromatin unwinding and increased gene expression of genes repressed in the H3K27 wild type. Additionally, a focal gain of methylation at other loci results in decreased gene expression elsewhere. Created with BioRender.com