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生物大分子国家重点实验室

周政 博士 研究员 博士生导师

中科院生物物理研究所,生物大分子卓越创新中心 生物大分子国家重点实验室,研究组长 中国科学院大学岗位教授

研究方向:染色质结构动态与表观遗传调控

电子邮件:zhouzh@ibp.ac.cn

电 话:010-64889862

通讯地址:北京市朝阳区大屯路15号(100101)

英文版个人网页:http://english.ibp.cas.cn/en_sourcedb_ibp/rck/EN_xsszmZ/202005/t20200519_341357.html

简 历:

  1992 - 1999  湖南师范大学,学士,硕士

  1999 - 2003  中国科学院上海生物化学与细胞生物学研究所,博士

  2003 - 2011  美国国立卫生研究院癌症研究所(NIH, NCI), 博士后

  2011 -          中国科学院生物物理研究所,研究员

  2012            中国科学院-诺和诺德长城教授奖

获奖及荣誉:

社会任职:

研究方向:

  真核生物的多种生命活动,如DNA复制、基因转录、DNA损伤修复、基因组稳定性维持等,均受到表观遗传机制的调控。染色质的动态变化调节DNA的折叠方式,是表观遗传调控的重要基础。DNA和组蛋白的分子结构、组成形式的改变能够造成染色质结构的动态变化,并与众多表观因子(如组蛋白变体、组蛋白伴侣、组蛋白修饰酶、染色质重塑复合物、非编码RNA等)一起调控染色质动态,确保生命活动的有序进行。本课题组致力于研究染色质动态的调控及其表观遗传功能。其主要发现包括组蛋白变体的识别机制、"核小体编辑"的基本规律、DNA损伤修复途径的决定机制等。

"核小体编辑"是染色质重构复合物催化组蛋白变体H2A.Z替换常规H2A,并将H2A.Z精准定位到基因组特定区域的过程,其功能异常与癌症等多种疾病密切相关。我们希望阐明核小体编辑的作用机制,实现核小体编辑的人工操控(图一)。细胞对DNA损伤修复途径的决定机制对于基因组稳定性维持至关重要,DNA损伤"合成致死"效应的发现,催生了PAPR抑制剂等一线抗癌药物。我们希望研究细胞选择不同修复途径进行DNA损伤修复的作用机制,寻找新的药物靶点用于抗癌药物的研发(图二)。

  我们将运用结构生物学、生物化学、生物物理学、酵母遗传学、单分子力谱等方法开展上述研究。

承担项目情况:

代表论著:

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.OPEN

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.OPEN

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.OPEN

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.OPEN

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.OPEN

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. OPEN

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. OPEN

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. OPEN

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.OPEN

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.OPEN

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. OPEN

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.OPEN

Invited Review

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

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)OPEN

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)OPEN

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

(资料来源:周政研究员,2023-07-05)

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