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)

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. Wenyan Li^#, Jie Hu^#, Feng Song^#, Juan Yu^#, Xin Peng, Shuming Zhang, Lin Wang, Mingli Hu, Jia-Cheng Liu, Yu Wei, Xue Xiao, Yan Li, Dongyu Li, Hui Wang, Bing-Rui Zhou, Linchang Dai, Zongjun Mou, Min Zhou, Haonan Zhang, Zheng Zhou, Huidong Zhang, Yawen Bai, Jin-Qiu Zhou, Wei Li, Guohong Li* & Ping Zhu*. Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction. Cell Research. (2024)

2. Ping Chen*, Guohong Li*, Wei Li*. Nucleosome Dynamics Derived at the Single-Molecule Level Bridges Its Structures and Functions. JACS Au, 4, 866-876. (2024)

3. Jicheng Zhao^#, Jie Lan^#, Min Wang^#, Cuifang Liu^#, Zheng Fang, Aoqun Song, Tiantian Zhang, Liang Wang, Bing Zhu, Ping Chen*, Juan Yu*, Guohong Li*. H2AK119ub1 differentially fine-tunes gene expression by modulating canonical PRC1- and H1-dependent chromatin compaction. Molecular Cell, 84, 1191-1205.e1197. (2024)

4. Chao-Pei Liu^#, Zhenyu Yu^#, Jun Xiong^#, Jie Hu^#, Aoqun Song^#, Dongbo Ding^#, Cong Yu, Na Yang, Mingzhu Wang, Juan Yu, Peini Hou, Kangning Zeng, Zhenyu Li, Zhuqiang Zhang, Xinzheng Zhang, Wei Li, Zhiguo Zhang, Bing Zhu*, Guohong Li*, Rui-Ming Xu*. Structural insights into histone binding and nucleosome assembly by chromatin assembly factor-1. Science, 381, eadd8673. (2023)

5. Cuifang Liu^#, Juan Yu^#, Aoqun Song^#, Min Wang, Jiansen Hu, Ping Chen, Jicheng Zhao* & Guohong Li*. Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction. Nat Commun, 14. (2023)

6. Li Huang^#, Youwang Wang^#, Haizhen Long^#*, Haoqiang Zhu, Zengqi Wen, Liwei Zhang, Wenhao Zhang, Zhenqian Guo, Longge Wang, Fangyi Tang, Jie Hu, Keyan Bao, Ping Zhu*, Guohong Li* and Zheng Zhou. Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1. Molecular Cell, 83, 2884-2895.e2887. (2023)

7. Yuting Liu^#, Kehui Wang^#, Li Huang^#, Jicheng Zhao, Xinpeng Chen, Qiang Wu, Zhouliang Yu*, Guohong Li*. Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice. Science China-Life Sciences, 65, 1881-1889. (2022)

8. Rui Hu ^#, Cuifang Liu ^#, Wenlong Lu, Guanghao Wei, Dapeng Yu, Wei Li, Ping Chen, Guohong Li*, Qing Zhao*. Probing the Effect of Ubiquitinated Histone on Mononucleosomes by Translocation Dynamics Study through Solid-State Nanopores. Nano Letters, 22, 888-895. (2022)

9. Cuifang Liu^#, Jicheng Zhao^#, and Guohong Li*. Preparation and Characterization of Chromatin Templates for Histone Methylation Assays. Methods in Molecular Biology, 2529, 91-107. (2022)

10. Yang Yang^#, Liwei Zhang*^#, Chaoyang Xiong, Jun Chen, Li Wang, Zengqi Wen, Juan Yu, Ping Chen, Yanhui Xu, Jingji Jin, Yong Cai* and Guohong Li*. HIRA complex presets transcriptional potential through coordinating depositions of the histone variants H3.3 and H2A.Z on the poised genes in mESCs. Nucleic Acids Research, 50, 191-206. (2022)

11. Ping Chen*, Wei Li* and Guohong Li. Structures and Functions of Chromatin Fibers. Annual Review of Biophysics, 50, 95-116. (2021)

12. Kehui Wang*, Yuting Liu*, Zhouliang Yu*, Bo Gu, Jie Hu, Li Huang, Xiao Ge, Lingyi Xu, Mengyu Zhang, Jicheng Zhao, Mingli Hu, Rongrong Le, Qiang Wu, Sheng Ye, Shaorong Gao, Xiaodong Zhan, Rui-Ming Xu, and Guohong Li^#. Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle. Cell Reports, 37, 109987. (2021)

13.Guohong Li*. The 3D organization of genome in the nucleus: from the nucleosome to the 4D nucleome. Science China-Life Sciences, 63, 791-794. (2020)

14. Juan Yu^#, Chaoyang Xiong^#, Baowen Zhuo^#, Zengqi Wen, Jie Shen, Cuifang Liu, Luyuan Chang, Kehui Wang, Min Wang, Chenyi Wu, Xudong Wu, Xueqing Xu*, Haihe Ruan*, and Guohong Li*. Analysis of Local Chromatin States Reveals Gene Transcription Potential during Mouse Neural Progenitor Cell Differentiation. Cell Reports, 32, 107953. (2020)

(From Guohong Li, August 28, 2024)