Packing the massive DNA polymer into a small and compact size structure within the nucleus is facilitated by nucleosomal proteins known as H2A, H2B, H3 and H4. In a typical nucleosome, the DNA is wrapped into two turns around the histone octamer core of four histone partners; H3-H4 tetramer and two H2A-H2B dimers. These proteins are known to undergo a variety of posttranslational modifications such as phosphorylation, methylation, acetylation and ubiquitination, which play crucial roles in regulating chromatin dynamics, gene expression and DNA repair. We are interested in understanding how these modifications achieve their function by chemically preparing homogeneously modified histones to support biochemical, biophysical and proteomic studies. For example, we have reported the efficient synthesis of monoubiquitinated H2B at Lys120 and Lys34 and studied its role in stem cell differentiation, structural analysis with known DUBs such as the SAGA deubiquitinating module and to find new proteins that interact with the modified chromatin.
