Dr. Jikui Song | University of California, Riverside
Professor bio:
Dr. Jikui Song obtained his Ph.D. degree in biochemistry from the University of Wisconsin-Madison. During his graduate training and subsequent effort in the Center for Eukaryotic Structural Genomics, he worked with Dr. John L Markey to investigate the protein structure-function relationships using NMR spectroscopy. He then received his postdoctoral training in Dr. Dinshaw J Patel’s laboratory at Memorial Sloan-Kettering Cancer Center, where he investigated the structural basis of protein complexes involved in epigenetic regulation. He joined the Department of Biochemistry at UC Riverside as a faculty member in 2012. Since then, he has investigated the structural basis of various epigenetic mechanisms and their link to human diseases, as well as the molecular basis of host-pathogen interactions, using integrated structural and biochemical methods.
Abstract:
DNA methylation is an evolutionarily conserved mechanism that regulates gene expression and genome stability. In mammals, establishment of DNA methylation is mainly achieved by de novo DNA methyltransferases DNMT3A and DNMT3B. Precise regulation of DNMT3A/DNMT3B functions is essential for orchestrating proper DNA methylation landscape across the genome, which governs cell fate determination and development. Mutation of DNMT3A is linked to cancers (e.g. AML and paragangliomas) and developmental disorders (e.g. Tatton-Brown-Rahman syndrome), while mutation of DNMT3B is associated with the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. Our recent study, through combined structural, biochemical and cellular analysis, uncovered the molecular basis for DNMT3A- and DNMT3B- mediated DNA methylation, and revealed how disease mutations of DNMT3A and DNMT3B lead to aberrant substrate binding and DNA methylation activities in vitro and in cells. These advances provide a basis for the development of novel therapeutic strategies against DNA methylation-linked human diseases.
