New publication in "J. Biol. Chem."

New publication in "J. Biol. Chem."

The protein lysine methyltransferases NSD1 and NSD2 dimethylate H3K36 and both enzymes are frequently mutated in cancers. We report in this paper that the NSD2 T1150A cancer mutation is hyperactive and unexpectedly discovered that it can introduce up to H3K36me3 in biochemical assays and in human cells. This is a very relevant finding as different methylation states of H3K36 trigger distinct biological responses. Molecular Dynamics experiments showed that H3K36me3 formation is possible due to an enlarged active site pocket of T1150A and loss of critical contacts which regulate the product specificity of NSD2. Bioinformatics analyses suggest that the aberrant generation of H3K36me3 by NSD2 T1150A could cause differential gene expression in cancer cells by antagonizing H3K27me3 mediated gene silencing.