Seminar "Organic chemistry for epigenetic studies"
Title: "Organic chemistry for epigenetic studies"
Speaker: Prof. Akimitsu Okamoto, Research Center for Advanced Science and Technology, The University of Tokyo
Methylation/demethylation of cytosine in DNA is an important epigenetic modification of the genome, and this process plays a crucial role in the regulation of developmental gene expression. Much effort has gone into developing a simple reaction that can be used for the detection of 5mC and 5hmC. We have developed the sequence-specific osmium complex formation at 5mC, using a bipyridine-attached adenine derivative. The osmium complex formation clearly distinguished 5mC from C, which was applied to visualization of a specific methylation in a single cell. Changes in the methylation status depending on the conditions of ions in the cell culture environment were visualized. We have also developed the oxidation of 5hmC using a dinuclear peroxotungstate for the discrimination of 5hmC from its epigenetic precursors, C and 5mC in DNA. The mass spectrum of the oxidation product obtained from the 5hmC-containing DNA indicated the formation of trihydroxylated thymine in DNA. The tungsten oxidation products induced the incorporation of adenine into the complementary site in a primer extension, and made it possible to detect 5hmC in a DNA sequence of interest in a conventional DNA sequencing analysis. These inorganic analyses of epigenetically modified DNA will provide beneficial information on the design of a powerful method for 5mC/5hmC scanning and typing to solve the mystery of the initialization of gene function through methylation/demethylation.