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报告题目：Genome Organization from the Ground Up -- Deciphering Molecular Mechanisms via a Near-atomistic Chromatin Model
报告时间：2023-02-13 10:00
报告人： 林星程 博士后研究员
Massachusetts Institute of Technology
报告地点：思明校区曾呈奎楼B311（现场报告）
报告摘要：
The three-dimensional genome organization lays the foundation for biological processes involving gene expression and epigenetic regulation. Nevertheless, it is unclear how the genome is structured and regulated at the molecular level. There is a heated debate over the existence of chromatin fibril structure and its regulation by multiple epigenetic regulators. Controversy also remains on the solid or liquid properties of chromatin subject to different environmental conditions. Recent computational advances have enabled direct simulations of biomolecules to reveal their structural mechanisms. However, the large size of chromatin molecules poses a significant challenge to fully sample their functional motions. Here, building upon our recently developed near-atomistic chromatin model, we integrated multiple computational chemistry techniques to examine the structural details of large chromatin systems. Our study of a tetranucleosome, the fundamental unit of chromatin, captures multiple irregular chromatin structures that emerge as intermediates of two chromatin folding pathways. Our further study of a dodecameric nucleosomal array quantitatively reproduces the force-extension curve measured by magnetic tweezers. The simulation also reveals a more complicated folding landscape of chromatin under tension than a stacked-unstacked two-state transition. Additional simulations of multiple poly-nucleosome arrays reveal a stable interdigitated configuration, thereby suggesting a mechanism initiating the sol-gel transition of chromatin. Finally, we show that Polycomb repressive complex 2 (PRC2), a critical epigenetic modification enzyme, can cooperatively loop DNA via allosteric communication and bridge non-adjacent nucleosomes to spread histone modifications. Our work reconciles the stability of different chromatin conformations under in vitro and in vivo environments and uncovers mechanistic insights on the impact of epigenetic regulators on genome organization.。
报告人简介：
林星程，2011年毕业于厦门大学物理系，本科时师从王矫教授完成毕业设计。2011-2018年于美国Rice University和Center for Theoretial Biological Physics获得计算生物物理博士学位。师从José Onuchic教授，并同时受到Peter Wolynes教授 和Herbert Levine教授的指导，从事protein dynamics, protein structure prediction, immunology等方面的工作。2018-2023年于Massachusetts Institute of Technology化学系Bin Zhang教授实验室从事博士后研究工作，从事chromatin dynamics, epigenetics, protein-DNA interactions等相关研究工作。2023年八月起，他将会加入NC State University物理系和生物信息学中心建立研究课题组，从事DNA, RNA, epigenetic regulation，以及genome方面的研究。
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