Defining a cytoplasmic role for a histone methyltransferase in C. elegans muscle

• William Snyder, Biological Sciences, University of Delaware

• Jessica Tanis, Biological Sciences, University of Delaware

The histone lysine methyltransferase SETDB1 trimethylates lysine 9 on histone 3 (H3K9me3), which leads to the formation of heterochromatin, silences gene expression, and impacts three-dimensional chromatin structure. We are using the C. elegans model system to define a new physiological role for MET-2, the worm homolog of SETDB1. Previous lab members imaged adult C. elegans that express functional GFP-tagged MET-2 from the endogenous locus and observed that MET-2::GFP localized to the cytoplasm of the body-wall muscles (BWMs) as well as nuclei of germ cells and embryos. Knockout of MET-2 or sequestration of MET-2 in the body wall muscles. I explored whether levamisole hypersensitivity was dependent on MET-2’s catalytic activity and persistence through multiple generations. I observed that the catalytically deficient met-2 mutants are hypersensitive to levamisole, suggesting that the hypersensitivity seen in met-2 animals is not due to a lack of methyltransferase activity. Since levamisole hypersensitivity is observed in animals with reduced ATP, we reasoned that MET-2 could impact the mitochondria. I crossed MET-2::GFP with mitochondrial marker TOMM-20::mKate to determine colocalization in body wall muscle cells. Imaging of these animals will enable me to determine if this histone methyltransferase is present in mitochondria.