PRC1 and chondroblastoma: This mutation is found in 95% of chondroblastomas and 92% of GCT, respectively in the H3F3B and H3F3A genes.213 Following the oncohistone paradigm, the H3K36me2/3 PTMs are reduced due to the inability of specific methyltransferases, namely SETD2, NSD1-NSD3, to deposit their marks.214,215 H3K36M reduces H3K36 methylation and increases nucleosome availability for PRC2 to deposit H3K27me3.214 The genome-wide increase in this repressive mark then induces a PRC1 redeployment which overall dilutes PRC1 at its canonical binding sites, leading to de-repression of self-renewal genes214,216 (Fig. 5c).