报告人： 何 俊 研究员  中国科学院广州生物医药与健康研究院

时   间： 2023年10月20日 11:00-12:00

地   点： 东十二楼 616 报告厅

邀请人：  马 聪 教授

报告人简介：何俊研究员在2006年获得清华大学学士学位，2012年获得伦敦Institute of Cancer Research博士学位。之后分别在伦敦Francis Crick Institute和UCB Pharma担任博士后和资深科学家。2019年入职中国科学院广州生物医药与健康研究院建立课题组，任研究员，博士生导师，获得中科院高层次人才项目，并兼任中国生物物理协会冷冻电子显微学分会委员。课题组主要致力于研究染色质动态调控的功能及机制，重点关注与肿瘤发展密切相关的重要大分子机器复合物，通过在多尺度上对这些复合物的高分辨率结构解析和功能机制研究，探索其在细胞命运调控网络中的功能和相互作用规律，在分子水平上理解其参与肿瘤发生发展的致病机理。独立以后以通讯作者（共同）在Cell Research，Nature Microbiology和 Nature Communication等期刊上发表相关工作，并承担国家自然科学基金和广东省自然科学基金等多项科研任务。

报告摘要：In Saccharomyces cerevisiae, cryptic transcription is prevented by the activity of Sin3 histone deacetylase (HDAC) complex Rpd3S in coding regions. Rpd3S is carried by the transcribing RNA polymerase II (RNAPII) to deacetylate and stabilize chromatin. Despite its fundamental importance, the mechanisms of Rpd3S deacetylating nucleosomes and regulating chromatin dynamics remain elusive. Here, we determined several cryo-EM structures of Rpd3S in complex with nucleosome core particles (NCP), including the H3/H4 deacetylation states, the alternative deacetylation state, the linker tightening state, and a state in which Rpd3S co-exists with the Hho1 linker histone on NCP. These states demonstrate that Rpd3S utilizes a conserved Sin3 basic surface to progress through the nucleosomal DNA in a left-handed superhelical manner, guided by its interactions with the chemical mimic of H3K36 methylation and the extra-nucleosomal DNA linkers to target acetylated H3K9 and sample other histone tails. Furthermore, our structures illustrate that Rpd3S reconfigures the DNA linkers and poises the NCP for Hho1 engagement, potentially unraveling how Rpd3S and Hho1 work in tandem for gene silencing.