EZH2 and glioma: A rigorous examination of histone H3 amino acid substitutions using in vitro biochemical assays, HEK-293 cell culture, and murine brain stem glioma models found that the K27M mutation can inactivate the polycomb repressive complex 2 (PRC2) via methionine/isoleucine-specific hydrophobic interactions with the active site of enhancer of zeste homolog 2 (EZH2) [20].