Recombinant Mononucleosomes H3.1 (K4M)
In vivo, histones are wrapped around by DNA in chromatin. Therefore, nucleosomes are more physiologically relevant substrates than histones and histone-derived peptides for in vitro studies. More importantly, some histone methyltransferases are significantly more active, as well as specific, when using nucleosomal substrates in HMT assays, such as DOT1L and NSD family enzymes. Nucleosomes are also widely used in histone methyltransferase screening assays to identify small molecular inhibitors for drug discovery. Histones are linked to tumorigenesis primarily through alterations in their PTMs and the enzymes regulating these modifications, suggesting that they might disrupt the reading, writing, and/or erasing of these marks. Mutations in histone H3 occur with high genetic penetrance within rare pediatric gliomas and sarcomas. In H3 variants, the mutation is most often a lysine-to-methionine (K-M) mutation, occasionally glycine mutations (G34R/V/W/L) occur too. According to researchers, mutations at H3K4: out of a total of 9 mutations at this site, 8 were a K4M/I substitution. More K-to-M/I mutations were observed, raising the possibility that the functional effects associated with known K-to-M/I changes (that is, function in a dominant fashion to block the methylation of corresponding lysines on wild type histones) may extend to additional contexts.