• 姓      名:    朱冰
• 职      务:   
• 职      称:    研究员
• 通讯地址:   

简历 & 研究组工作摘要

教育经历

1999年 中国科学院上海植物生理研究所分子遗传学博士

1995年 中国水稻研究所遗传学硕士

1992年 浙江大学生物科学与技术系学士

工作经历

2014年- 中国科学院生物物理所研究员

2011-2014年 北京生命科学研究所高级研究员

2006-2011年 北京生命科学研究所研究员

2002-2006年 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

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

研究概述

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。

研究论文(*: Corresponding author)

1. Zhao Z., Lan M., Li J., Dong Q., Li X., Liu B., Li G., Wang H., Zhang Z.*, and Zhu B*., The proinflammatory cytokine TNFalpha induces DNA demethylation-dependent and -independent activation of interleukin-32 expression. J Biol Chem, 2019. 294(17): p. 6785-6795. PMID: 30824537

2. Zhang T., Guan X., Choi U.L., Dong Q., Lam M.M.T., Zeng J., Xiong J., Wang X., Poon T.C.W., Zhang H., Zhang X., Wang H., Xie R., Zhu B., and Li G.*, Phosphorylation of TET2 by AMPK is indispensable in myogenic differentiation. Epigenetics Chromatin, 2019. 12(1): p. 32. PMID: 31164154

3. Hou P., Huang C., Liu C.P., Yang N., Yu T., Yin Y., Zhu B.*, and Xu R.M.*, Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding. Structure, 2019. 27(5): p. 837-845 e3. PMID: 30827843

4. Fu H., Liu N., Dong Q., Ma C., Yang J., Xiong J., Zhang Z., Qi X., Huang C., and Zhu B.*, SENP6-mediated M18BP1 deSUMOylation regulates CENP-A centromeric localization. Cell Res, 2019. 29(3): p. 254-257. PMID: 30631152

5. Du W., Dong Q., Zhang Z., Liu B., Zhou T., Xu R.M., Wang H., Zhu B.*, and 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(22): p. 8907-8917. PMID: 31018966

6. Wu F., Zhang J., Shang E., Zhang J., Li X., Zhu B., and 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: p. 642. PMID: 30627529

7. 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 G.L., Wang Z., Wang H., Gao S., and Zhu B.*, Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature, 2018. 564(7734): p. 136-140. PMID: 30487604

8. 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.*, and 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(4): p. 695-708 e4. PMID: 30291027

9. 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.*, and Chen T.*, Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration. Cell Stem Cell, 2018. 23(4): p. 487-500 e6. PMID: 30122476

10. Dong Q., Li X., Wang C.Z., Xu S., Yuan G., Shao W., Liu B., Zheng Y., Wang H., Lei X., Zhang Z.*, and Zhu B.*, Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing. Proc Natl Acad Sci U S A, 2018. 115(17): p. E4013-E4022. PMID: 29636421

11. 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.*, and 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(19): p. 7423-7436. PMID: 29559556

12. Huang C., Yang F., Zhang Z., Zhang J., Cai G., Li L., Zheng Y., Chen S., Xi R.*, and Zhu B.*, Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Nature Communications, 2017. 8(1): p. 1649. PMID: 29158494

13. Li M., Dong Q., and Zhu B.*, Aurora Kinase B Phosphorylates Histone H3.3 at Serine 31 during Mitosis in Mammalian Cells. J Mol Biol, 2017. 429(13): p. 2042-2045. PMID: 28137420

14. Xiong J., Zhang Z.*, Chen J., Huang H., Xu Y., Ding X., Zheng Y., Nishinakamura R., Xu G.L., Wang H., Chen S., Gao S., and Zhu B.*, Cooperative Action between SALL4A and TET Proteins in Stepwise Oxidation of 5-Methylcytosine. Mol Cell, 2016. 64(5): p. 913-925. PMID: 27840027

15. Shang E., Zhang J., Bai J., Wang Z., Li X., Zhu B., and 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 (Camb), 2016. 52(43): p. 7028-31. PMID: 27161847

16. Sun L., Zhang Y., Zhang Z., Zheng Y., Du L., and Zhu B.*, Preferential Protection of Genetic Fidelity within Open Chromatin by the Mismatch Repair Machinery. J Biol Chem, 2016. 291(34): p. 17692-705. PMID: 27382058

17. Dai C., Li W., Tjong H., Hao S., Zhou Y., Li Q., Chen L., Zhu B., Alber F.*, and Jasmine Zhou X.*, Mining 3D genome structure populations identifies major factors governing the stability of regulatory communities. Nat Commun, 2016. 7: p. 11549. PMID: 27240697

18. Fu W., Liu N., Qiao Q., Wang M., Min J., Zhu B., Xu R.M.*, and Yang N.*, Structural Basis for Substrate Preference of SMYD3, a SET Domain-containing Protein Lysine Methyltransferase. J Biol Chem, 2016. 291(17): p. 9173-80. PMID: 26929412

19. Sun J., Wei H.M., Xu J., Chang J.F., Yang Z., Ren X., Lv W.W., Liu L.P., Pan L.X., Wang X., Qiao H.H., Zhu B., Ji J.Y., Yan D., Xie T., Sun F.L.*, and Ni J.Q.*, Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation. Nat Commun, 2015. 6: p. 8856. PMID: 26581759

20. 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., and 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(4): p. 379-93. PMID: 25637356

21. Zhou T., Xiong J., Wang M., Yang N., Wong J., Zhu B., and Xu R.M.*, Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2. Mol Cell, 2014. 54(5): p. 879-86. PMID: 24813944

22. Mao Z., Pan L., Wang W., Sun J., Shan S., Dong Q., Liang X., Dai L., Ding X., Chen S., Zhang Z.*, Zhu B.*, and Zhou Z.*, Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z. Cell Res, 2014. 24(4): p. 389-99. PMID: 24613878

23. Su X., Zhu G., Ding X., Lee S.Y., Dou Y., Zhu B., Wu W.*, and Li H.*, Molecular basis underlying histone H3 lysine-arginine methylation pattern readout by Spin/Ssty repeats of Spindlin1. Genes Dev, 2014. 28(6): p. 622-36. PMID: 24589551

24. Yuan G., Ma B., Yuan W., Zhang Z., Chen P., Ding X., Feng L., Shen X., Chen S., Li G., and Zhu B.*, Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases. J Biol Chem, 2013. 288(43): p. 30832-42. PMID: 24019522

25. Huang C., Zhang Z., Xu M., Li Y., Li Z., Ma Y., Cai T., and Zhu B.*, H3.3-H4 tetramer splitting events feature cell-type specific enhancers. PLoS Genet, 2013. 9(6): p. e1003558. PMID: 23754967

26. Yang N.*, Wang W., Wang Y., Wang M., Zhao Q., Rao Z., Zhu B.*, and Xu R.M.*, 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(44): p. 17954-9. PMID: 23077255

27. 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 X.J., Gao S.*, and Zhu B.*, Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science, 2012. 337(6097): p. 971-5. PMID: 22923582

28. Xu M., Chen S.*, and Zhu B.*, Investigating the cell cycle-associated dynamics of histone modifications using quantitative mass spectrometry. Methods Enzymol, 2012. 512: p. 29-55. PMID: 22910201

29. Xu M., Wang W., Chen S.*, and Zhu B.*, A model for mitotic inheritance of histone lysine methylation. EMBO Rep, 2011. 13(1): p. 60-7. PMID: 22056817

30. Wang W., Chen Z., Mao Z., Zhang H., Ding X., Chen S., Zhang X., Xu R., and Zhu B.*, Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes. EMBO Rep, 2011. 12(11): p. 1160-6. PMID: 21960006

31. Yang P., Wang Y., Chen J., Li H., Kang L., Zhang Y., Chen S., Zhu B.*, and 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(5): p. 791-801. PMID: 21433225

32. Wu H., Chen X., Xiong J., Li Y., Li H., Ding X., Liu S., Chen S., Gao S., and Zhu B.*, Histone methyltransferase G9a contributes to H3K27 methylation in vivo. Cell Res, 2011. 21(2): p. 365-7. PMID: 21079650

33. Yuan W., Xu M., Huang C., Liu N., Chen S., and Zhu B.*, H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem, 2011. 286(10): p. 7983-9. PMID: 21239496

34. Xu M., Long C., Chen X., Huang C., Chen S.*, and Zhu B.*, Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. Science, 2010. 328(5974): p. 94-8. PMID: 20360108

35. Jia G., Wang W., Li H., Mao Z., Cai G., Sun J., Wu H., Xu M., Yang P., Yuan W., Chen S., and Zhu B.*, A systematic evaluation of the compatibility of histones containing methyl-lysine analogues with biochemical reactions. Cell Res, 2009. 19(10): p. 1217-20. PMID: 19770845

36. Yuan W., Xie J., Long C., Erdjument-Bromage H., Ding X., Zheng Y., Tempst P., Chen S., Zhu B.*, and 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(23): p. 15701-7. PMID: 19332550

37. Moniaux N., Nemos C., Deb S., Zhu B., Dornreiter I., Hollingsworth M.A., and Batra S.K.*, The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression. PLoS One, 2009. 4(9): p. e7077. PMID: 19771162

38. Pavri R., Zhu B., Li G., Trojer P., Mandal S., Shilatifard A., and Reinberg D.*, Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell, 2006. 125(4): p. 703-17. PMID: 16713563

39. Adelman K., Wei W., Ardehali M.B., Werner J., Zhu B., Reinberg D., and Lis J.T.*, Drosophila Paf1 modulates chromatin structure at actively transcribed genes. Mol Cell Biol, 2006. 26(1): p. 250-60. PMID: 16354696

40. Zhu B., Zheng Y., Pham A.D., Mandal S.S., Erdjument-Bromage H., Tempst P., and Reinberg D.*, Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol Cell, 2005. 20(4): p. 601-11. PMID: 16307923

41. Zhu B., Mandal S.S., Pham A.D., Zheng Y., Erdjument-Bromage H., Batra S.K., Tempst P., and Reinberg D.*, The human PAF complex coordinates transcription with events downstream of RNA synthesis. Genes Dev, 2005. 19(14): p. 1668-73. PMID: 16024656

42. Jost J.P.*, Oakeley E.J., Zhu B., Benjamin D., Thiry S., Siegmann M., and Jost Y.C., 5-Methylcytosine DNA glycosylase participates in the genome-wide loss of DNA methylation occurring during mouse myoblast differentiation. Nucleic Acids Res, 2001. 29(21): p. 4452-61. PMID: 11691933

43. Zhu B., Benjamin D., Zheng Y., Angliker H., Thiry S., Siegmann M., and Jost J.P.*, 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(9): p. 5031-6. PMID: 11296268

44. Zhu B., Zheng Y., Angliker H., Schwarz S., Thiry S., Siegmann M., and Jost J.P.*, 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(21): p. 4157-65. PMID: 11058112

45. Zhu B., Zheng Y., Hess D., Angliker H., Schwarz S., Siegmann M., Thiry S., and Jost J.P.*, 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(10): p. 5135-9. PMID: 10779566

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.