1992 - 1999  Hunan Normal University, B.Sc & M.Sc in Biochemistry and Molecular Biology

1999 - 2003  Shanghai Institute of Biochemistry and Cell biology, Chinese Academy of Sciences, Ph.D. in Biochemistry and Molecular Biology

2003 - 2011  National Institutes of Health, National Cancer Institute, Visiting / Research Fellow

2011 -          Principal Investigator, National Laboratory of Biomacromolecules. Institute of Biophysics, Chinese Academy of Sciences

Epigenetic regulation controls dynamic changes in chromatin structure to modulate cellular events related to DNA accessibility, such as DNA replication, gene transcription, DNA damage repair, and the maintenance of genomic stability. Histone variants regulate these dynamic changes, serving as key players in epigenetic regulation. My lab aims to understand the principles of establishing and maintaining distinct chromatin states. We try to address how histone H2A variants regulate chromatin structure and gene expression in concert with histone chaperones, post-translational modifications, chromatin remodelers, and how their dysfunction links to human diseases. We combine a wide range of state-of-the-art techniques, including structural biology, biochemistry, biophysics, yeast genetics, single-molecule spectroscopy, and computational biology, to pursue research in two directions:

1. Nucleosome Editing: Investigating how remodeling complexes replace conventional histones with variants and control nucleosome editing. Precise positioning of H2A variants regulates gene expression, linking to diseases like cancer. Understanding nucleosome editing mechanisms could advance epigenetic editing technologies.

2. DNA Double-Strand Break Repair Pathway Choice: Examining how cells select repair pathways for DNA damage. The synthetic lethality effect of DNA damage informs cancer treatment, leading to drugs like PARP inhibitors. Clarifying DNA repair mechanisms can identify new drug targets and foster anticancer drug development.

1. Huang L, Wang Y, Long H, Zhu H, Wen Z, Zhang L, Zhang W, Guo Z, Wang L, Tang F, Hu J, Bao K, Zhu P, Li G, Zhou Z. (2023) Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1. Mol Cell. In press.

2. Chen J, Lu Z, Gong W, Xiao X, Feng X, Li W, Shan S, Xu D, Zhou Z. (2022) Epstein-Barr virus protein BKRF4 restricts nucleosome assembly to suppress host antiviral response. Proc Natl Acad Sci USA.119 (37): e2203782119.

3. Shi L, Huang L, Long H, Song A, Zhou Z. (2022) Structural basis of nucleosomal H4K20 methylation by methyltransferase SET8. FASEB J. 36(6):e22338.

4. Dai L, Dai Y, Han J, Huang Y, Wang L, Huang J, Zhou Z. (2021) Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin. Mol Cell. 81(13): 2765-2777.

5. Dai L, Xiao X, Pan L, Shi L, Xu N, Zhang Z, Feng X, Ma L, Dou S, Wang P, Zhu B, Li W, Zhou Z. (2021) Recognition of the inherently unstable H2A nucleosome by Swc2 is a major determinant for unidirectional H2A.Z exchange. Cell Rep. 35(8):109183.

6. Zhou N, Shi L, Shan S, Zhou Z. (2021) Molecular basis for the selective recognition and ubiquitination of centromeric histone H3 by yeast E3 ligase Psh1. J Genetics Genomics. 48(6):463-472.

7. Zhou M, Dai L, Li C, Shi L, Huang Y, Guo Z, Wu F, Zhu P, Zhou Z. (2021) Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2, EMBO J. 40(1): e105907.

8. Huang Y, Sun L, Pierrakeas L, Dai L, Pan L, Luk E, Zhou Z. (2020) Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing. Proc Natl Acad Sci USA. 117(7): 3543–3550.

9. Dai Y, Zhang F, Wang L, Shan S, Gong Z, Zhou Z. (2019) Structural basis for shieldin complex subunit 3-mediated recruitment of the checkpoint protein REV7 during DNA double-strand break repair. J Biol Chem. 295(1):250-262.

10. Dai L, Xu N, Zhou Z. (2019) NMR investigations on H2A-H2B heterodimer dynamics conferred by histone variant H2A.Z. Biochem Biophys Res Commun. 518(4):752-758.

11. Wang Y, Liu S, Sun L, Xu N, Shan S, Wu F, Liang X, Huang Y, Luk E, Wu, C, Zhou Z. (2019) Structural insights into histone chaperone Chz1-mediated H2A.Z recognition and histone replacement. PLoS Biol. 17(5): e3000277.

12. Dai Y, Zhang A, Shan S, Gong Z, Zhou Z.(2018) Structural basis for recognition of53BP1 tandem Tudor domain by TIRR. Nat Commun. 9(1):2123.

13. Dai L, Xie X, Zhou Z. (2018) Crystal structure of the histone heterodimer containing histone variant H2A.Bbd. Biochem Biophys Res Commun. 503(3):1786-1791.

14. Liang X, Shan S, Pan L, Zhao J,Ranjan A, Wang F, Zhang Z, Huang Y, Feng H, Wei D, Huang L, Liu X, Zhong Q, Lou J, Li G, Wu C, Zhou Z. (2016) Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1. Nat Struct Mol Biol. 23(4):317-325.

15. Mao Z, Pan L, Wang W, Sun J, Shan S, Dong Q, Liang X, Dai L, Ding X, Chen S, Zhang Z, Zhu B, Zhou Z. (2014) Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z. Cell Res. 24(4):389–399.

Invited reviews

1. Xiao S, Wang Y, Shan S, Zhou Z. (2023) The interplay between viral molecular mimicry and host chromatin dynamics. Nucleus. 14(1): 2216560.

2. Huang Y, Dai Y, Zhou Z. (2020) Mechanistic and structural insights into histone H2A-H2B chaperone in chromatin regulation. Biochem J. 477 (17): 3367-3386. (review)

3. Huang Y, Zhou Z. (2018) Recent progress in histone chaperones associated with H2A-H2B type histones. Prog Biochem Biophys. 45(9): 971-980. (review)

4. Zhou J, Feng X, Zhou Z. (2015) Chromatin assembly of histone variants. Prog Biochem Biophys. 42(11):1003~1008. (review)

(From Zheng Zhou, September 14, 2024)