Native Proteomics: A Novel Platform to Study Nucleosome Modification Dynamics

While the genetic origins of many diseases, including cancer, are widely accepted, increasing evidence suggests that disruptions in the cell’s epigenetic machinery may be the key initiators in several types of cancer and other disorders.The nucleosome, the smallest repeating unit of chromatin, lies at the center of epigenetic regulation. It consists of ~147 bp of DNA wrapped around two copies of the core histones: H2A, H2B, H3, and H4. Nucleosomes can be modified by post-translational modifications (PTMs) that decorate histones and the recruitment of histone variants that with diverse biophysical properties. In this way, nucleosome remodeling can regulate key cellular processes such as transcription, cell repair, and replication, that are central to human health and disease. This research will develop a novel mass spectrometry approach to study the nucleosome modification dynamics, covalent histone modifications and histone variant substitutions that exert epigenetic control over a gene.