Recent high-throughput sequencing analyses have revealed high incidences of somatic histone lysine-to-methionine (K-to-M) mutations in multiple cancers. We have established fission yeast models in which the introduction of H3K9M or H3K36M transgenes abolishes the methylation of corresponding lysines on wild-type histones, thereby recapitulating the effects of these mutations in cancer cells. We are examining how these mutations regulate cellular functions and identifying pathways that can be targeted to selectively kill cells containing these oncogenic histone mutations.
