10/15/19 - 9:45 AM to 11:00 AM
Department Seminar: Professor Champak Chatterjee
Chemical approaches to investigate eukaryotic gene transcription
The Chatterjee lab develops new chemical tools to investigate the mechanistic roles of protein post-translational modifications in human gene regulation. The chemical modifications we study vary in complexity from the methylation and acetylation of lysine side-chains to their conjugation with small proteins, such as ubiquitin and the small ubiquitin-like modifier protein (SUMO).1 By employing a powerful combination of synthetic protein chemistry and molecular biology, called semisynthesis, we have produced uniformly and site-specifically ubiquitylated and sumoylated human histones and transcription factors in quantities that are inaccessible from cells.2,3 Biophysical and biochemical studies with these proteins have revealed the direct effects of sumoylation on chromatin structure and function, and identified new biochemical crosstalk between histone sumoylation and methylation.4 The semisynthetic methodologies and insights gained from mechanistic studies with modified histones will be presented and discussed in the context of RNA polymerase II-mediated gene transcription.
- Weller, C.E. et al. “Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins.” Nature Communications 2016, 12979.
- Dhall, A. et al. “Rapid semisynthesis of acetylated and sumoylated histone analogs.” Methods in Enzymology 2016, 574, 149-165.
- Hsu, P. et al. “Crystal structure of the COMPASS H3K4 methyltransferase catalytic module.” Cell 2018, 174, 1106-1116.
- Dhall, A. et al. “Chemically sumoylated histone H4 stimulates intranucleosomal demethylation by the LSD1-CoREST complex.” ACS Chemical Biology 2017,12, 2275-2280.
Professor Chatterjee's lab is particularly interested in understanding how simple chemical modifications of proteins, that are found from bacteria to humans, have dramatic effects on protein structure and function. Researchers use a combination of organic synthesis and molecular biology to make semisynthetic proteins modified at specific amino acids. By studying the structure and function of these semisynthetic proteins under well-defined conditions that mimic living cells, they are learning how specific modified proteins work inside human cells.
Professor Chatterjee received his undergraduate degree in chemistry from the University of Bombay, and a master's degree in organic chemistry from the Indian Institute of Technology in Bombay. He performed doctoral studies at the University of Illinois at Urbana-Champaign, where he studied the mechanism of lantibiotic biosynthesis and developed a keen interest in the biology of post-translational protein modification. His post-doctoral work in synthetic protein chemistry at Rockefeller University focused on understanding the mechanism by which ubiquitin stimulates histone methylation, and developing new methods for the site-specific modification of proteins with ubiquitin and ubiquitin-like proteins.