A mutation in histone H2B Represents a new class of oncogenic driver

The goal of this study was to determine the mechanism by which a glutamate to lysine mutation of histone H2B at amino acid 76 (H2B-E76K), found particularly in bladder and head and neck cancer, may promote the oncogenic program. Gene expression analysis and ATAC-seq reveals that expression of H2B-E76K in the normal mammary epithelial cell line MCF10A caused a significant drift in gene expression and fundamental changes in chromatin accessibility particularly at gene regulatory elements. Thus, mutations in the core histones that frequently occur in cancer may represent a new mechanism of epigenetic dysfunction that destabilizes the nucleosome, deregulates chromatin accessibility and alters gene expression to drive cellular transformation.