Determining the Substrate Selectivity of SUV39H

After synthesis, proteins undergo further alterations in the form of post-translational modifications (PTMs). One of the common types of PTMs present in the proteome is lysine methylation, catalyzed by lysine methyltransferases (KMTs). Much of the early research involving KMTs focused exclusively on histone proteins. In recent years, however, there has been a rapidly increasing list of methylated proteins with unknown enzymes performing these modifications. This project involves SUV39H1 which was the first KMT discovered. SUV39H1 has been shown to methylate the histone H3K9 and lead in gene repression. Another KMT, EZH2, is also involved in gene repression, but must methylate both a histone and non-histone protein to perform its function. It is unknown whether SUV39H1 requires a similar non-histone substrate for its repressing function. The goal of this project is to find the substrate selectivity of SUV39H1 by utilizing a lysine-oriented peptide library (K-OPL). This information would enable us to determine whether SUV39H1 methylates any non-histone proteins. To accomplish this goal, biochemistry and biology techniques were implemented to purify the desired protein and interpret its enzymatic activity.

Supervisor: Dr. Evan Cornett
Department: Biochemistry and Molecular Biology