Analyzing the Protein Interactome of Lysine Methyltransferase G9a in Drosophila melanogaster

Abstract

G9a is a conserved lysine methyltransferase that catalyzes H3K9me2, an epigenetic mark associated with repressed gene expression. The goal of this research project was to provide the first in-depth characterization of the Drosophila G9a protein interactome. Several novel Drosophila G9a interactors were identified, encompassing various interactions conserved in mammals. Tissue-specific analyses revealed enhanced enrichment of Notch regulators in the mushroom body, indicating a potential mechanism mediating G9a’s function in this cell type. Proteins Scm and CG9932 were maintained as highly specific G9a interactors across cell types, indicating a novel G9a-Scm-CG9932 protein complex. Functional validations of these interactors suggest roles for Scm and CG9932 in the context of G9a activity in the fat body. Taken together, the findings of this project have greatly improved our knowledge of G9a’s interactions partners in Drosophila and in doing so have shed light on the molecular mechanisms governing G9a activity in these organisms.