Protein arginine methyltransferases (PRMTs) play key roles in regulating a multitude of cellular events. The methylated arginine residue itself serves to alter protein-protein interactions or enzymatic activities that are essential to specific signaling pathways. In addition, arginine methylation plays an important role in the regulation of proteins by either preventing or promoting the posttranslational modification of other neighboring residues. In addition to being involved in crosstalk with acetylation and ubiquitination, arginine methylation can affect phosphorylation. Regardless of the type of methylation mark (ADMA, SDMA or ?-MMA), the mechanism by which methylated arginines influence neighboring phosphorylated residues is unknown. In the case of the histone H3 tail, the addition of a phosphate group to serine-10 forms a salt bridge with arginine-8. The objective of this application is to explore the crosstalk between arginine-8 methylation and serine-10 phosphorylation in histone H3 whereby one modification alters the other. To accomplish this work, we will use both in vitro and in vivo methylation and phosphorylation assays. This work will elucidate the role of arginine methylation on phosphorylation, which is essential for understanding cellular biochemistry and physiological function.
Our goal is to investigate the role of arginine-8 methylation on serine-10 phosphorylation in histone H3. Histone proteins act as spools for DNA, influencing DNA function, particularly gene expression. Inappropriate gene expression causes a large number of diseases including cancer.
