Leveraging epigenetics research to understand chromatin biology and transcription regulation
Histone methyltransferase complexes play an important role in regulating chromatin and gene expression. KMT2C and KMT2D are two members of a specific class of molecules that methylate lysine residues on histone 3 (H3K4). These complexes are some of the most commonly mutated pan-cancer genes and are often perturbed in neurological disease. Our laboratory is focused on understanding how H3K4 methyltransferases regulate the epigenetic landscape. Determining the factors that control turnover, function and recruitment of these complexes will guide new therapeutic approaches.
Research in our laboratory is concentrated in epigenetics with the goal of understanding chromatin biology and the regulation of transcription. More specifically, we design studies to gain insight into the biology of the KMT2C/D (MLL3/4) histone H3K4 methyltransferase complexes and their relevant subunits including KDM6A (UTX).
Building from our initial experiments aimed at identifying the interactome of these complexes, we are exploring how various binding partners contribute to localization and function of these H3K4 methyltransferase complexes across the genome. We use next generation sequencing technologies, combining ChIP-seq, RNA-seq, to assess the transcriptomic landscape in the context of H3K4 methylation.
We are also interested in exploring upstream players that might regulate the transcription of methyltransferase complex components or control their protein stability. Using CRISPR screening approaches, we’ve identified putative targets for further validation. Considering that mutations in H3K4 methyltransferase complex components drive changes in protein expression in many diseases, understanding whether and how we might modulate protein levels as a therapeutic approach is of particular interest.
Dr. Herz earned his BS and PhD from the University of Heidelberg in Germany and completed his postdoctoral training at the Stowers Institute for Medical Research in Kansas City, MO, before joining the Department of Cell & Molecular Biology and the Comprehensive Cancer Center at St. Jude in 2015. He leads an innovative and growing research program that focuses on epigenetic components that are responsible for regulating gene expression in cells and are often mutated in various cancers and neurodevelopmental disorders.
Molecular biologists, biochemists, and geneticists with diverse expertise in the field of chromatin biology