1991 - 1995  Wuhan University, Department of Virology, B.Sc.

1995 - 1998  Beijing Medical University, Department of Biophysics, M.Sc.

1998 - 2003  Max-Planck-Institute for Cell Biology/Heidelberg University, Ph.D.

2003 - 2006  Postdoctoral Research Associate, HHMI/UMDNJ/RWJMS

2006 - 2009  Postdoctoral Research Associate and Research Scientist, HHMI/NYU

2009 -　　     Principal Investigator, CAS Institute of Biophysics

2015  Young Leading Talents on Science and Technology Innovation, the Ministry of Science and Technology of China

2015  National Natural Science Fund for Distinguished Young Scholar, China

2017  HHMI “International Research Scholar”

2017  The 10^th C.C.Tan (Jia-Zhen Tan) Life Science Award (谈家桢生命科学创新奖)

2015  Chinese Academy of Sciences, Department of Biochemistry and Molecular Biology, deputy director of the Department

2017 《Genome Biology》and 《JBC》, Editorial Board member

2018 《Sience China: Life Science》, Editorial Board member

The research in our group is mainly focusing on the epigenetic regulation of chromatin higher-order structures on transcription, and their biological functions in cell fate determination during programming and reprogramming of embryonic stem (ES) cells. Our research mainly includes three directions as follows:

1. Structure of 30-nm Chromatin Fibers and their epigenetic regulations

During programming and reprogramming of stem cells, the transcriptional signatures are regulated by epigenetic mechanisms, including DNA methylation, histone variants and histone modifications. In the meanwhile, the dynamics of chromatin structures, which correlate with the transcriptional activity of genes, can be regulated by many epigenetic factors. Although the structure of nucleosomes, the fundamental repeating unit of chromatin, is clear, which comprises 146 base pairs of DNA wrapped in 1.7 superhelical turns around an octamer of histones, there is still much discussion on the higher-order levels of chromatin structure, including 30-nm chromatin fiber, the second structural level of DNA organization. It has been clear that the plasticity of and the dynamics of higher-order chromatin fiber are key regulators of transcription and other biological processes inherent to DNA. Elucidating just how a nucleosomal array can be compacted into higher-order chromatin structures is central to understanding the dynamics of chromatin structure. In our group, we have developed the chromatin in-vitro reconstitution and structural analysis system with techniques including EM/Cryo-EM, AUC, single-molecule(sm)-magnetic tweezers, FRET/sm-FRET. We focus on the investigation on the 3D structure of 30-nm chromatin fibers, their structural plasticity/dynamics and epigenetic regulations.

2. The structure and function of chromatin in centromere

Centromeres are the specialized chromosomal loci that drive the assembly of the kinetochores and allow the accurate chromosome segregation during mitosis and meiosis. A unique histone H3 variant known as CENP-A, which is therefore proposed as the epigenetic mark of the centromere, is responsible for centromere identity. However, up to date, the composition and the structure of centromeric chromatin are still unclear. The studies on nucleosome composition, dynamic assembly, higher order chromatin organization, epigenetic regulation of CENP-A containing chromatin at centromeres during cell cycles remain rather limited. In our group, by using our established an in vitro chromatin reconstitution system together with the in vivo cell assay and the biophysical, biochemical, molecular biology techniques, we will extensively investigated the structure of centromeric nucleosome, the recognition and dynamic assembly of CENP-A on centromeres, the cooperatively regulation of CENP-A and other histone variants in nucleosome dynamics and higher-order chromatin structure of centromere, the dynamic deposition and maintenance of CENP-A throughout the cell cycle, the biological functions of centromere in stem cell biology and diseases such as cancer and ageing.

3. The Dynamic Interactions between Chromatin and Nuclear Envelope during Stem Cell Differentiation

In eukaryotic cell, other than the 30-nm fibers, chromatin can be hierarchically compacted into further complicated folding levels and organized in three dimensions via interacting with other nuclear structures within the nucleus. The nuclear lamina, a filamentous protein network that provides a structural scaffold for the inner nuclear membrane, has been shown to dynamically interact with specific chromatin domains and regulate gene expression and stem cell differentiation. Molecular mapping indicated that lamina-genome interactions are dynamic and play essential roles in the regulation of gene expression programs during lineage commitment and terminal differentiation. However, it remains unclear by which mechanisms the chromatin organization and nuclear architecture might regulate the gene expression. Our group is investigating the establishment and maintenance of chromatin underlining the nuclear envelope/nuclear lamina and their dynamic changes during cell lineage commitment, terminal differentiation and diseases such as progeria.

1. Zengqi Wen*, Liwei Zhang, Haihe Ruan*, and Guohong Li*. Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells. Nucleic Acids Research 48(11), 5939-5952. (2020)

2. Jicheng Zhao^#, Min Wang^#, Luyuan Chang, Juan Yu, Aoqun Song, Cuifang Liu, Wenjun Huang, Tiantian Zhang, Xudong Wu, Xiaohua Shen, Bing Zhu and Guohong Li. H1-Compacted Chromatin Facilitates Propagation of H2AK119ub1 by RYBP/YAF2-PRC1 Complex during Cell Division. Nature Cell Biology 22(4), 439-452. (2020)

3. Haizhen Long^#, Liwei Zhang^#, Mengjie Lv^#, Zengqi Wen^#, Wenhao Zhang, Xiulan Chen, Peitao Zhang, Tongqing Li, Luyuan Chang, Caiwei Jin, Guozhao Wu, Xi Wang, Fuquan Yang, Jianfeng Pei, Ping Chen, Raphael Margueron, Haiteng Deng, Mingzhao Zhu* and Guohong Li*. H2A.Z Facilitates Licensing and Activation of Early Replication Origins. Nature 577(7791), 576-581. (2020)

4. Liang Wang^#, Mingli Hu^#, Mei-Qing Zuo, Jicheng Zhao, Di Wu, Li Huang, Yongxin Wen, Yunfan Li, Ping Chen, Xinhua Bao, Meng-Qiu Dong, Guohong Li*, and Pilong Li*. Rett Syndrome-Causing Mutations Compromise MeCP2-mediated Liquid-Liquid Phase Separation of Chromatin. Cell Research 2020 Feb 28. doi: 10.1038/s41422-020-0288-7. (2020)

5. Chaoyang Xiong^#, Zengqi Wen^#, Juan Yu, Jun Chen, Chao-Pei Liu, Xiaodong Zhang, Ping Chen, Rui-Ming Xu and Guohong Li. UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells. BMC Biology 16(1), 110. doi: 10.1186/s12915-018-0573-9. (2018)

6. Yan Wang^#, Haizhen Long^#, Juan Yu^#, Liping Dong^#, Michel Wassef, Baowen Zhuo, Xia Li, Jicheng Zhao, Min Wang, Cuifang Liu, Zengqi Wen, Luyuan Chang, Ping Chen, Qian-fei Wang, Xueqing Xu, Raphael Margueron* and Guohong Li*. Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells. BMC Biology 16(1), 107. doi: 10.1186/s12915-018-0568-6. (2018)

7. Ping Chen^#, Liping Dong^#, Mingli Hu, Yi-Zhou Wang, Xue Xiao, Zhongliang Zhao, Jie Yan, Peng-Ye Wang, Danny Reinberg, Ming Li*, Wei Li* and Guohong Li*. Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level. Molecular Cell 71(2), 284-293. (2018)

8. Wei Li^#, Ping Chen^#, Juan Yu, Liping Dong, Dan Liang, Jianxun Feng, Jie Yan, Peng-Ye Wang, Qing Li, Zhiguo Zhang, Ming Li* and Guohong Li*. FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription. Molecular Cell 64(1), 120-133. (2016)

9. Qian Zhao^#, Jiqin Zhang^#, Ruoyu Chen^#, Lina Wang^#, Bo Li, Hao Cheng, Xiaoya Duan, Haijun Zhu, Wei Wei, Jiwen Li, Qihan Wu, Jing-Dong J. Han, Wenqiang Yu, Shaorong Gao, Guohong Li* and Jiemin Wong*. Dissecting the Precise Role of H3K9 Methylation in Crosstalk with DNA Maintenance Methylation in Mammals. Nature Communications (2016)

10. Qianglin Fang^#, Ping Chen^#, Mingzhu Wang, Junnan Fang, Na Yang, Guohong Li*, Rui-Ming Xu*. Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome. Elife 5(Pii), e11911 (2016)

11. Junnan Fang, Yun Wei, Yuting Liu, Wenqiang Deng, Zhouliang Yu, Li Huang,Yan Teng,Ting Yao, Qinglong You, Haihe Ruan, Ping Chen, Rui-Ming Xu, and Guohong Li. Structural Transitions of Centromeric Chromatin Coordinate the Cell Cycle-dependent Recruitment of CENP-N. Genes and Development 29, 1058-1073 (2015).

12. Zhouliang Yu, Xiang Zhou, Wenjing Wang, Wenqiang Deng, Junnan Fang, Hao Hu, Zichen Wang, Shangze Li, Lei Cui, Jing Shen, Linhui Zhai, Shengyi Peng, Jiemin Wong, Shuo Dong, Zengqiang Yuan, Guangshuo Ou, Xiaodong Zhang, Ping Xu, Jizhong Lou, Na Yang, Ping Chen, Rui-Ming Xu, and Guohong Li. Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell cycle-dependent deposition at centromeres. Developmental Cell 32(1), 68-81. (2015)

13. Feng Song^#, Ping Chen^#, Dapeng Sun, Mingzhu Wang, Dan Liang, Ruiming Xu, Ping Zhu* and Guohong Li*. Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetra-nucleosomal units. Science 344(6182), 376-380. (Research article, 2014）

14. Ping Chen^#, Jicheng Zhao^#, Yan Wang^#, Haizhen Long, Dan Liang, Haiyong Zhao, Zengqi Wen, Wei Li, Xia Li, Li Huang, Hongli Feng,Ping Zhu, Ming Li, Qainfei Wang, and Guohong Li. Variant histone H3.3 functionally counteracts with H2A.Z to activate gene transcription. Genes and Development, 27(19), 2109-2124. (2013)

15. Chao-pei Liu^#, Chaoyang Xiong^#, Mingzhu Wang, Zhouliang Yu, Na Yang, Ping Chen, Zhiguo Zhang, Guohong Li* and Rui-Ming Xu*. Structure of the variant histone H3.3-H4 heterodimer in complex with its chaperone DAXX. Nature Structural and Molecular Biology 19(12)，1287-1292. (2012)

(From Guohong Li, July 8, 2020)