The Effect of Oncohistone Mutations on the Combinatorial Epigenome

Whole genome sequencing efforts highlighted recurrent cancer-associated mutations in the genes encoding the core histones comprising the nucleosome structure. High-grade pediatric gliomas often carry gain-of-function mutations in the H3 gene (‘oncohistones’), which result in extensive deregulation of the chromatin landscape. We apply our single-molecule imaging platform and advance chromatin profiling strategies to decipher chromatin incorporation and combinatorial epigenetic patterns associated with mutant nucleosomes. Our research reveals multiple epigenetic nodes directly affected by oncohistones and points toward promising new therapeutic approaches.