The Effect of Phosphorylation on Histone Tail Recognition by Epigenetic Reader Protein HP1

The study of epigenetics deals with the factors that turn genes on or off at the right time. Proper maintenance of post translational modifications (PTMs) on histones is a critical feature of epigenetic regulation. Dysregulation is implicated in numerous diseases, including several types of cancer. The structure of chromatin and the degree to which DNA is packaged determine which genes will or will not be expressed. DNA is wrapppped around histone octamers in order to form the nucleosome, which then tightly packs together to form chromosomes. Post translational modifications are used to control genes turning on and off by binding to other proteins. These PTMs are recognized by non-enzymatic reader proteins. In this study, we investigate the effect of two PTMs: methylation and phosphorylation. The focus of our study is binding trimethyllysine on histone tail 3 to the HP1 chromodomain in the aromatic cage. One of the tyrosines in the aromatic cage can also be posted translationally modified to phosphotyrosine. Reader proteins that bind methylated lysine have a common motif of an aromatic cage in which cation- interactions are the driving forces for binding methylated lysine. We aim to determine the influences that phosphorylation has on binding via two strategies: by studying the complex HP1 protein itself along with a Beta-Hairpin model system. We have hypothesized that the cation- interactions would be weakened overall due to the phosphorylation of tyrosine. After running cCircular dDichroism experiments on the B-hairpin model system, the data suggests that the B-hairpin containing phosphotyrosine was less folded and less stabilized; therefore data received supported our hypothesis