报 告 人：李佳斌 博士（中国科学技术大学）
Jiabin Li received B.S. degree in 2009 from University of Science and Technology of China (USTC), and his PH.D. degree in Organic chemistry from Tsinghua University in January 2015. Then, he joined the School of Life Sciences, Tsinghua University as a Postdoctoral Fellow. In February 2017, he joined the School of Life Sciences, USTC as a Research Associate Professor. He is mainly engaged in the chemical synthesis and application of histone post-translational modifications (PTMs). In recent years, he has developed several new chemical methods for the preparation of modified histones and accomplished the chemical synthesis of all four core histones. A number of histone PTMs were efficiently synthesized, including methylation, acetylation, ubiquitination. Using the chemically modified histones, he also devoted himself to the studies of the molecular mechanisms and biochemical functions of histone PTMs.
Histone PTMs play important roles in regulating the structure and dynamics of chromatin, as well as DNA-driven cellular processes. Their dysregulation is closely related to the appearance and progression of many diseases. A key to understand the function and molecular mechanism of histone PTMs is the preparation of homogenously modified histones, which has been a challenge in this field. Therefore, we developed a practical method for the one-pot ligation of peptide hydrazides and the TFA-labile auxiliary mediated ligation for site-specific ubiquitination. By making use of the new methods, a number of histone PTMs, including methylation, acetylation and ubiquitination on all four core histones, were efficiently prepared on a tens of milligram scale. Furthermore, the synthetic histones were applied in in vitro structural and functional studies for deciphering the “histone code”. We resolved the first structure of H2BK34Ub-containing nucleosome with single particle cryo-EM analysis. Besides, we revealed the plasticity of DNA repair factor 53BP1 or deubiquitinase USP51 recognition in both modification sites of H2A and types of ubiquitin chains with an array of site-specifically ubiquitinated H2As, which provided valuable insight into the H2A ubiquitination drived DNA double strand breaks repair.