水木清华生命科学讲座系列第67期
1.Topic: Chromatin and Epigenetics
2.Photo：
3.Introduction of speaker：
李国红博士1972年出生于湖北大冶，1995年毕业于武汉大学病毒系，2003年获德国海德堡大学生物学博士，2003-2010在美国霍华德休斯医学研究院（HMMI）从事博士后研究。2010年全职回到中国科学院生物物理研究所生物大分子国家重点实验室工作，现任生物大分子国家重点实验室副主任。
李国红博士主要致力于染色质高级结构及其表观遗传调控机理的研究，并取得了一系列研究成果：在国际上首次解析了高精度的30nm染色质纤维的三维冷冻电镜结构，揭示了一种全新的左手双螺旋结构；并发现“四聚核小体”结构是染色质纤维折叠中的一个重要中间结构单元，并受组蛋白分子伴侣FACT的调控；此外，还揭示了一系列重要组蛋白变体的识别、组装及其对染色质高级结构调控的分子机理。李国红博士先后入选和获得中科院“百人计划”、国家杰出青年基金、中组部万人计划创新领军人才、HHMI国际研究学者、“谈家桢生命科学创新奖”。
4. Title and unit
Speaker: Guohong Li, Ph.D.
Investigator
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing
5.Abstract:
Eukaryotic DNA is hierarchically packaged into chromatin to fit inside the nucleus, in which the accessibility of DNA is dependent on the packing density of chromatin. Dynamics of chromatin structures plays a critical role in transcriptional regulation and all other DNA related biological processes. Previously, we reported the 11 Å resolution cryo-electron microscopy (cryo-EM) structures of 30 nm chromatin fibers reconstituted in the presence of linker histone H1, which reveals a left-handed double helix twisted by the repeating tetra-nucleosomal structural units. Using single-molecule force spectroscopy, we reveal that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. The stability of the tetranucleosomal unit is negatively regulated by the histone chaperone FACT (Facilitates Chromatin Transcription) in vitro. Interestingly, we further revealed that FACT has dual functions in breaking nucleosome and maintaining its integrity during DNA replication and transcription. In addition, we also demonstrated that formation of 30-nm chromatin fibers greatly facilitates the faithful propagation of H2AK119ub1 by RYBP-PRC1 during cell divisions. In summary, our study demonstrates that the tetranucleosome is a novel regulatory structural unit of chromatin fibers beyond the nucleosome, and provides crucial mechanistic insights into functions of chromatin fibers in transcriptional regulation and epigenetic inheritance.
日期：5月24日（周四）15:00-16:00
地点：清华大学医学科学楼B323
