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创新研究群体项目获得者

朱冰  博士 研究员 博士生导师  

国家“杰出青年科学基金”获得者
中科院生物物理所,副所长
生物大分子国家重点实验室,研究组长

研究方向:表观遗传学

电子邮件:zhubing@ibp.ac.cn

电       话:010-64888832

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/faculty/index_18316.html?json=http://www.ibp.cas.cn/sourcedb_ibp_cas/cn/ibpexport/EN_xsszmZ/202005/t20200519_5582953.json

课题组网站:http://www.ibp.cas.cn/zhubLab/

简       历:

  1992             浙江大学,生物科学与技术系,学士

  1995             中国水稻研究所,遗传学,硕士

  1999             中国科学院上海植物生理研究所,分子遗传学,博士

  1999 - 2002  瑞士弗雷德里克·米歇尔研究所,Jean-Pierre Jost博士实验室,博士后

  2002 - 2006  美国霍华德·休斯医学院/新泽西医学与牙医学大学/罗伯特-伍德-约翰逊医学院,Danny Reinberg博士实验室,博士后

  2006 - 2011  北京生命科学研究所,研究员

  2011 - 2014  北京生命科学研究所,高级研究员

  2014 - 至今  中国科学院生物物理所,研究员

获奖及荣誉:

 

社会任职:

 

研究方向:

  表观遗传学的可塑性和可继承性

  多细胞生物的多种细胞类型拥有同一基因组体,却各不相同,并拥有各自独特的基因表达谱。这被认为是由表观遗传学机制实现的对DNA承载的遗传信息的精细调控。表观遗传学信息需要同时具有可塑性和一定的可继承性,以确保不同类型细胞可以得到分化,又可以在分化后维持稳定。本实验室的研究兴趣为:

  1. 表观遗传信息的建立与维持机制

  多种组蛋白修饰和DNA甲基化是经典表观遗传现象的重要调控因子,本实验室试图通过结合生物化学,定量蛋白质组学,高通量基因组分析和高通量筛选来鉴定并理解参与表观遗传信息的建立与维持的新机制。

  2. 染色质修饰酶的活性调节

  大量的染色质修饰酶已被鉴定,但对它们催化活性的调节机理研究较少。染色质修饰酶常被认为是机械性的催化机器,然而近期的研究表明染色质修饰酶更可能是聪明的艺术家,可以视基因转录状态的不同和染色质环境的不同调节自己的活性,以谱写不同的修饰曲调。对染色质修饰酶活性调节的研究不仅有助于对表观遗传学机制的理解,也有助于更好的设计干预染色质修饰酶活性的小分子化合物。因为多个染色质修饰酶被认为是潜在的药物靶标。

承担项目情况:

 

代表论著:

  1. Ming X, Zhang Z, Zou Z, Lv C, Dong Q, He Q, Yi Y, Li Y, Wang H, Zhu B*. Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration. Cell Res. 2020 Online ahead of print.

  2. Zhao J, Wang M, Chang L, Yu J, Song A, Liu C, Huang W, Zhang T, Wu X, Shen X, Zhu B, Li G. RYBP/YAF2-PRC1 complexes and histone H1-dependent chromatin compaction mediate propagation of H2AK119ub1 during cell division. Nat Cell Biol. 2020; 22: 439-452.

  3. Zhang T, Zhang Z, Dong Q, Xiong J*, Zhu B*. Histone H3K27 acetylation is dispensable for enhancer activity in mouse embryonic stem cells. Genome Biol. 2020; 21: 45.

  4. Li C, Chen Y, Zhu H, Zhang X, Han L, Zhao Z, Wang J, Ning L, Zhou W, Lu C, Xu L, Sang J, Feng Z, Zhang Y, Lou X, Bo X, Zhu B, Yu C, Zheng M, Li Y, Sun J, Shen Z. Inhibition of histone deacetylation by MS-275 alleviates colitis by activating the vitamin D receptor. J Crohns Colitis. 2020 Online ahead of print.

  5. Zhang T, Guan X, Choi UL, Dong Q, Lam MMT, Zeng J, Xiong J, Wang X, Poon TCW, Zhang H, Zhang X, Wang H, Xie R, Zhu B, Li G. Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics Chromatin. 2019; 12: 32.

  6. Du W, Dong Q, Zhang Z, Liu B, Zhou T, Xu RM, Wang H, Zhu B, Li Y. Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1. J Biol Chem. 2019; 294: 8907-8917.

  7. Zhao Z, Lan M, Li J, Dong Q, Li X, Liu B, Li G, Wang H, Zhang Z*, Zhu B*. The proinflammatory cytokine TNF-α induces DNA demethylation-dependent and -independent activation of interleukin-32 expression. J Biol Chem. 2019; 294: 6785-6795.

  8. Hou P, Huang C, Liu CP, Yang N, Yu T, Yin Y, Zhu B*, Xu RM*. Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding. Structure. 2019; 27: 837-845.

  9. Fu H, Liu N, Dong Q, Ma C, Yang J, Xiong J, Zhang Z, Qi X, Huang C, Zhu B*. SENP6-mediated M18BP1 deSUMOylation regulates CENP-A centromeric localization. Cell Res. 2019; 29: 254-257.

  10. Wu F, Zhang J, Shang E, Zhang J, Li X, Zhu B, Lei X. Synthesis and Evaluation of a New Type of Small Molecule Epigenetic Modulator Containing Imidazo[1,2-b][1,2,4]triazole Motif. Front Chem. 2018 6: 642.

  11. Li Y, Zhang Z, Chen J, Liu W, Lai W, Liu B, Li X, Liu L, Xu S, Dong Q, Wang M, Duan X, Tan J, Zheng Y, Zhang P, Fan G, Wong J, Xu GL, Wang Z, Wang H, Gao S, Zhu B*. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature. 2018; 564: 136-140.

  12. Hong S, Zhang Z, Liu H, Tian M, Zhu X, Zhang Z, Wang W, Zhou X, Zhang F, Ge Q, Zhu B, Tang H, Hua Z, Hou B. B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen. Immunity. 2018; 49: 695-708.

  13. Yu Z, Jiang K, Xu Z, Huang H, Qian N, Lu Z, Chen D, Di R, Yuan T, Du Z, Xie W, Lu X, Li H, Chai R, Yang Y, Zhu B, Kunieda T, Wang F*, Chen T*. Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration. Cell Stem Cell. 2018; 23: 487-500.

  14. Dong Q, Li X, Wang CZ, Xu S, Yuan G, Shao W, Liu B, Zheng Y, Wang H, Lei X, Zhang Z*, Zhu B*. Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing. Proc Natl Acad Sci U S A. 2018; 115: E4013-E4022.

  15. Li X, Shang E, Dong Q, Li Y, Zhang J, Xu S, Zhao Z, Shao W, Lv C, Zheng Y, Wang H, Lei X, Zhu B*, Zhang Z*. Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway. J Biol Chem. 2018; 293: 7423-7436.

  16. Huang C, Yang F, Zhang Z, Zhang J, Cai G, Li L, Zheng Y, Chen S, Xi R*, Zhu B*. Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Nature Commun. 2017; 8: 1649.

  17. Li M, Dong Q, Zhu B*. Aurora Kinase B Phosphorylates Histone H3.3 at Serine 31 during Mitosis in Mammalian Cells. J Mol Biol. 2017; 429: 2042-2045.

  18. Xiong J, Zhang Z*, Chen J, Huang H, Xu Y, Ding X, Zheng Y, Nishinakamura R, Xu GL, Wang H, Chen S, Gao S, Zhu B*. Cooperative Action between SALL4A and TET Proteins in Stepwise Oxidation of 5-Methylcytosine. Mol Cell. 2016; 64: 913-925.

  19. Sun L, Zhang Y, Zhang Z, Zheng Y, Du L, Zhu B*. Preferential Protection of Genetic Fidelity within Open Chromatin by the Mismatch Repair Machinery. J Biol Chem. 2016; 291: 17692-17705.

  20. Dai C, Li W, Tjong H, Hao S, Zhou Y, Li Q, Chen L, Zhu B, Alber F*, Zhou JX*. Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities. Nat Commun. 2016; 7: 11549.

  21. Shang E, Zhang J, Bai J, Wang Z, Li X, Zhu B, Lei X*. Syntheses of [1,2,4]triazolo[1,5-a]benzazoles enabled by the transition-metal-free oxidative N-N bond formation. Chem Commun. 2016; 52: 7028-7031.

  22. Fu W, Liu N, Qiao Q, Wang M, Min J, Zhu B*, Xu RM*, Yang N*. Structural Basis for Substrate Preference of SMYD3, A SET Domain-containing Protein Lysine Methyltransferase. J Biol Chem. 2016; 291: 9173-9180.

  23. Sun J, Wei HM, Xu J, Chang JF, Yang Z, Ren X, Lv WW, Liu LP, Pan LX, Wang X, Qiao HH, Zhu B, Ji JY, Yan D, Xie T, Sun FL*, Ni JQ*. Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation. Nat Commun. 2015; 6: 8856.

  24. Liu N, Zhang Z, Wu H*, Jiang Y, Meng L, Xiong J, Zhao Z, Zhou X, Li J, Li H, Zheng Y, Chen S, Cai T, Gao S, Zhu B*. Recognition of H3K9 methylation by GLP is required for efficient establishment of H3K9 methylation, rapid target gene repression, and mouse viability. Genes Dev. 2015; 29: 379-393.

  25. Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM*. Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Mol Cell. 2014; 54: 879-586.

  26. 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*. Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z Cell Res. 2014; 24: 389-399.

  27. Su X, Zhu G, Ding X, Lee SY, Dou Y, Zhu B, Wu W*, Li H*. Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1. Genes Dev. 2014; 28: 622-636.

  28. Yuan G, Ma B, Yuan W, Zhang Z, Chen P, Ding X, Feng L, Shen X, Chen S, Li G, Zhu B*. Histone H2A Ubiquitination Inhibits the Enzymatic Activity of H3 Lysine 36 Methyltransferases. J Biol Chem. 2013; 288: 30832-30842.

  29. Huang C, Zhang Z, Xu X, Li Y, Li Z, Ma Y, Cai T, Zhu B*. H3.3-H4 tetramer splitting events feature cell-type specific enhancers. Plos Genet. 2013; 9: e1003558.

  30. Yang N*, Wang W, Wang Y, Wang M, Zhao Q, Rao Z, Zhu B*, Xu RM*. Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1. Proc Natl Acad Sci U S A. 2012; 109: 17954-17959.

  31. Yuan W, Wu T, Fu H, Dai C, Wu H, Liu N, Li X, Xu M, Zhang Z, Niu T, Han Z, Chai J, Zhou XJ, Gao S*, Zhu B*. Dense chromatin activates Polycomb repressive complex 2 to regulate H3 Lysine 27 methylation. Science 2012; 337: 971-975.

  32. Xu M, Wang W, Chen S*, Zhu B*. A model for mitotic inheritance of histone lysine methylation. EMBO Rep. 2012; 13: 60-67.

  33. Wang W, Chen Z, Mao Z, Zhang H, Ding X, Chen S, Zhang X, Xu RM, Zhu B*. Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes. EMBO Rep. 2011; 12: 1160-1166.

  34. Yang P, Wang Y, Chen J, Li H, Kang L, Zhang Y, Chen S, Zhu B*, Gao S*. RCOR2 Is a Subunit of the LSD1 Complex That Regulates ESC Property and Substitutes for SOX2 in Reprogramming Somatic Cells to Pluripotency. Stem Cells 2011; 29: 791-801.

  35. Chen X, Xiong J, Xu M, Chen S*, Zhu B*. Symmetrical modification within a nucleosome is not required globally for histone lysine methylation. EMBO Rep. 2011; 12: 244-251.

  36. Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B*. H3K36 methylation antagonizes PRC2 mediated H3K27 methylation. J Biol Chem. 2011; 286: 7983-7989.

  37. Wu H, Chen X, Xiong J, Li Y, Li H, Ding X, Liu S, Chen S, Gao S, Zhu B*. Histone methyltransferase G9a contributes to H3K27 methylation in vivo. Cell Res. 2011; 21: 365-367.

  38. Xu M, Long C, Chen X, Huang C, Chen S*, Zhu B*. Partition of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. Science 2010; 328: 94-98.

  39. Jia G, Wang W, Li H, Mao Z, Cai G, Sun J, Wu H, Xu M, Yang P, Yuan W, Chen S, Zhu B*. A systematic evaluation of the compatibility of histones containing methyl-lysine analogues with biochemical reactions. Cell Res. 2009; 19: 1217-1220.

  40. Yuan W, Xie J, Long C, Erdjument-Bromage H, Ding X, Zheng Y, Tempst P, Chen S, Zhu B*, Reinberg D*. Heterogeneous nuclear ribonucleoprotein L Is a subunit of human KMT3a/Set2 complex required for H3 Lys-36 trimethylation activity in vivo. J Biol Chem. 2009; 284:15701-15707.

  41. Moniaux N, Nemos C, Deb S, Zhu B, Dornreiter I, Hollingsworth MA, Batra SK* (2009) The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression. PLoS One 4: e7077.

  42. Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, Reinberg D*. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 2006; 125: 703-717.

  43. Adelman K, Wei W, Ardehali MB, Werner J, Zhu B, Reinberg D, Lis JT*. Drosophila Paf1 modulates chromatin structure at actively transcribed genes. Mol Cell Biol. 2006; 26: 250-260.

  44. Zhu B, Zheng Y, Pham AD, Mandal SS, Erdjument-Bromage H, Tempst P, Reinberg D*. Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell 2005; 20: 601-611.

  45. Zhu B, Mandal SS, Pham AD, Zheng Y, Erdjument-Bromage H, Batra SK, Tempst P, Reinberg D*. The human PAF complex coordinates transcription with events downstream of RNA synthesis. Genes Dev. 2005; 19: 1668-1673.

  46. Jost JP*, Oakeley EJ, Zhu B, Benjamin D, Thiry S, Siegmann M, Jost YC. 5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation. Nucleic Acids Res. 2001; 29: 4452-4461.

  47. Zhu B, Benjamin D, Zheng Y, Angliker H, Thiry S, Siegmann M, Jost JP*. Overexpression of 5-methylcytosine DNA glycosylase in human embryonic kidney cells EcR293 demethylates the promoter of a hormone-regulated reporter gene. Proc Natl Acad Sci U S A. 2001; 98: 5031-5036.

  48. Zhu B, Zheng Y, Angliker H, Schwarz S, Thiry S, Siegmann M, Jost JP*. 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence. Nucleic Acids Res. 2000; 28: 4157-4165.

  49. Zhu B, Zheng Y, Hess D, Angliker H, Schwarz S, Siegmann M, Thiry S, Jost JP*. 5-methylcytosine-DNA glycosylase activity is present in a cloned G/T mismatch DNA glycosylase associated with the chicken embryo DNA demethylation complex. Proc Natl Acad Sci U S A. 2000; 97: 5135-5139.

Invited reviews (*: Corresponding author):

  1. Huang C. and Zhu B.*, Roles of H3K36-specific histone methyltransferases in transcription: antagonizing silencing and safeguarding transcription fidelity. Biophys Rep, 2018. 4(4): p. 170-177. PMID: 30310854

  2. Wang C., Zhu B.*, and Xiong J.*, Recruitment and reinforcement: maintaining epigenetic silencing. Sci China Life Sci, 2018. 61(5): p. 515-522. PMID: 29564598

  3. Xiong J., Zhang Z., and Zhu B.*, Polycomb "polypacks" the chromatin. Proc Natl Acad Sci U S A, 2016. 113(52): p. 14878-14880. PMID: 27994153

  4. Wang C.-Z. and Zhu B.*, You are never alone: crosstalk among epigenetic players. Science Bulletin, 2015. 60(10): p. 899-904.

  5. Huang C. and Zhu B.*, H3.3 turnover: a mechanism to poise chromatin for transcription, or a response to open chromatin? Bioessays, 2014. 36(6): p. 579-84. PMID: 24700556

  6. Huang C., Xu M., and Zhu B.*, Epigenetic inheritance mediated by histone lysine methylation: maintaining transcriptional states without the precise restoration of marks? Philos Trans R Soc Lond B Biol Sci, 2013. 368(1609): p. 20110332. PMID: 23166395

  7. Talbert P.B., Ahmad K., Almouzni G., Ausio J., Berger F., Bhalla P.L., Bonner W.M., Cande W.Z., Chadwick B.P., Chan S.W., Cross G.A., Cui L., Dimitrov S.I., Doenecke D., Eirin-Lopez J.M., Gorovsky M.A., Hake S.B., Hamkalo B.A., Holec S., Jacobsen S.E., Kamieniarz K., Khochbin S., Ladurner A.G., Landsman D., Latham J.A., Loppin B., Malik H.S., Marzluff W.F., Pehrson J.R., Postberg J., Schneider R., Singh M.B., Smith M.M., Thompson E., Torres-Padilla M.E., Tremethick D.J., Turner B.M., Waterborg J.H., Wollmann H., Yelagandula R., Zhu B., and Henikoff S.*, A unified phylogeny-based nomenclature for histone variants. Epigenetics Chromatin, 2012. 5: p. 7. PMID: 22650316

  8. Yuan G. and Zhu B.*, Histone variants and epigenetic inheritance. Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 2012. 1819(3-4): p. 222-229. PMID: 24459724

  9. Zhu B.* and Reinberg D.*, Epigenetic inheritance: uncontested? Cell Res, 2011. 21(3): p. 435-41. PMID: 21321606

  10. Wu H. and Zhu B.*, Split decision: why it matters? Frontiers in Biology, 2011. 6(2): p. 88-92. DOI: 10.1007/s11515-011-1040-y

  11. Xu M. and Zhu B.*, Nucleosome assembly and epigenetic inheritance. Protein Cell, 2010. 1(9): p. 820-9. PMID: 21203924  

图书:

  译著:《表观遗传学》。主译:朱冰,孙方霖。科学出版社。85万字,2009年。  

Book chapter:

  1. Xu M, Chen S*, Zhu B*. Investigating the cell cycle-associated dynamics of histone modifications using quantitative mass spectrometry. In: Methods in Enzymology. 512: Nucleosomes, Histones & Chromatin, Eds. Carl Wu, C David Allis, Elsevier Academic Press INC, USA, pp29-55. 2012.

  2. Nan Liu, Zhu B*. Regulation of PRC2 activity. In: Polycomb Group Proteins. Ed. Vincenzo Pirrotta, Elsevier Academic Press INC, USA, pp225-258. 2017.

  

(资料来源,朱冰研究员,2019-11-25)