THE INTERACTION BETWEEN ARGININE METHYLATION AND SERINE PHOSPHORYLATION IN HISTONE H3
Mariel Grace Mendoza, Cecilia Zurita-Lopez.
California State University, Los Angeles, Los Angeles, CA.
Specific combinations of posttranslational modifications on the N-terminal tail of histone proteins can determine patterns of gene expression. It has been demonstrated that protein arginine methyltransferases methylate arginine residues in FOXO1 and BAD proteins, and this modification blocks Akt-mediated serine phosphorylation. We expect that a similar crosstalk is occurring in histone H3, where adjacent arginine 8 (H3R8) and serine 10 (H3S10) residues are methylated and phosphorylated, respectively. We propose that arginine methylation can inhibit phosphorylation of neighboring serine residues regardless of the kinase phosphorylating the substrate. Through this mechanism, H3R8 methylation can serve as an inhibitory modification that is capable of regulating gene expression by impeding phosphorylation. In vitro studies using peptides based on histone H3 and full-length recombinant H3 will be used to demonstrate this interplay. Specific methylated H3R8 and phosphorylated H3S10 will be detected via immunoblot analyses, mass spectrometry, and radioactive assays. Investigating the crosstalk between posttranslational modifications on histone proteins provides a deeper understanding of gene regulation, and can potentially serve as a novel therapeutic target for drug development.