Background
K36M mutant of histone H3.3 is an "oncohistone" identified in more than 90% of chondroblastoma, a rare type of benign tumor caused by cartilage-producing cells. The mutant inhibits at least two H3K36 methyltransferases MMSET/WHSC1 and SETD2, triggering a depletion of H3K36 methylation and an increase of H3K27 trimethylation. H3.3K36M mutant proteins further alters expression of various genes including BMP2 that regulate oncogenesis and chondrogenesis. Chondrocytes expressing H3.3K36M exhibit several cancer-associated cellular phenotypes, including increased ability to form colonies, resistance to staurosporine-induced apoptosis, and defects in differentiation.
Cellular location
Nucleus
