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Bing Zhu, Ph.D, Prof.

Principal Investigator, IBP Deputy Director

National Laboratory of Biomacromolecules, IBP

Epigenetics

E-mail:zhubing@ibp.ac.cn ,Tel:010-64888832

Fax:010-64871293,Zip code:100101

Chinese personal homepageGroup Website 

Biography & Introduction

Education

1999- Ph.D., Shanghai Institute of Plant Physiology, Chinese Academy of Sciences

1995- M.S., China National Rice Research Institute

1992- B.S., Zhejiang University, China

Professional Experience

2014-   Investigator, Institute of Biophysics, Chinese Academy of Sciences

2011-2014  Associate Investigator, National Institute of Biological Sciences, Beijing, China

2006-2011  Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2002-2006  Research Teaching Specialist, Lab of Dr. Danny Reinberg, Howard-Hughes Medical Institute/University of Medicine and Dentistry of New Jersey/ Robert Wood Johnson Medical School

1999-2002  Research Fellow, Lab of Dr. Jean-Pierre Jost, Friedrich Miescher Institute, Switzerland

Research Description

Epigenetics: plasticity versus inheritabilitybingzhu

Our ultimate goal is to understand how we can qualify to be successful multi-cellular organisms. Successful multi-cellular organisms are required to achieve two simple tasks: 1. Cells should be able to alter their fate to generate distinct cell types for different functions, in a process termed differentiation; 2. Cells and their progenies should be able to maintain their fate when differentiation is no more required at the post-mitotic stages or during proliferation.

DNA is unarguably the carrier of genetic information. However, DNA sequence alone cannot explain how hundreds of cell types in a complex multi-cellular organism, such as a human individual can possess distinct transcription programs, while sharing the same genetic information. This is believed to be achieved by fine-tuning our genetic information with a so-called “epigenetic” system. To fulfill the two basic tasks challenging the multi-cellular organisms, epigenetic system must simultaneously offer dual characteristics, “Plasticity & Inheritability”. Plasticity allows the transformation of one genome into hundreds of epigenomes and transcriptomes, whereas inheritability permits the maintenance of every single epigenome and its corresponding transcriptome.

Mitotic inheritance of histone modification-based epigenetic information 

Several histone modifications have been shown to be critical in classic epigenetic phenomena, including Position effect variegation, Polycomb silencing and dosage compensation. However, how newly deposited histones acquire these modifications during/after DNA replication remains unclear. We attempt to address this important question using combinatory approaches by integrating biochemistry, quantitative mass spectrometry and high-throughput sequencing.

Enzymatic activity regulation of chromatin modifying enzymes 

Another important direction in our laboratory is to study the biochemical regulation of chromatin modifying enzymes. Despite the exponentially increasing number of studies about chromatin modifying enzymes, the mechanistic regulation of these enzymes is poorly understood. Therefore, we are interested in understanding the molecular mechanisms behind activation and antagonization of chromatin modifying enzymes. We believe this is an important direction for chromatin biology, not only because of mechanistic insights that can be derived from such studies, but also because a mechanistic understanding will contribute to guided small molecule inhibitor design for chromatin modifying enzymes. This goal is particularly important because many chromatin modifying enzymes, such as histone deacetylases (HDACs) and, more recently, PRC2, are being considered as potential drug targets.

Research publications (*: Corresponding author) 

1. 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.

2. 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.

3. 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; 913-925.

4. 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.

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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. Xiong J, Zhang Z, Zhu B*. Polycomb "polypacks" the chromatin. Proc Natl Acad Sci USA. 2016; 113: 14878-14880.

2. Wang CZ, Zhu B*. You are never alone: crosstalk among epigenetic players. Science Bulletin, 2015; 60: 899-904.

3. Huang C, Zhu B*. H3.3 turnover: A mechanism to poise chromatin for transcription, or a response to open chromatin? Bioessays, 2014; 36: 579-584

4. Huang C, Xu M, 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: 20110332

5. Talbert PB, Ahmad K, Almouzni G, Ausió J, Berger F, Bhalla PL, Bonner WM, Cande WZ, Chadwick BP, Chan SW, Cross GA, Cui L, Dimitrov SI, Doenecke D, Eirin-López JM, Gorovsky MA, Hake SB, Hamkalo BA, Holec S, Jacobsen SE, Kamieniarz K, Khochbin S, Ladurner AG, Landsman D, Latham JA, Loppin B, Malik HS, Marzluff WF, Pehrson JR, Postberg J, Schneider R, Singh MB, Smith MM, Thompson E, Torres-Padilla ME, Tremethick DJ, Turner BM, Waterborg JH, Wollmann H, Yelagandula R, Zhu B, Henikoff S*. A unified phylogeny-based nomenclature for histone variants. Epigenet Chromatin 2012; 5: 7

6. Yuan G, Zhu B*. Histone variants and epigenetic inheritance. BBA-Gene Regul Mech. 2012; 1819: 222-229

7. Zhu B*, Reinberg D*. Epigenetics inheritance: Uncontested? Cell Res. 2011; 21: 435-441

8. Wu H, Zhu B*. Split decision: why it matters? Front Biol. 2011; 6: 88-92

9. Xu M, Zhu B*. Nucleosome assembly and epigenetic inheritance. Protein Cell 2010; 1: 820-829

Book

A translation:《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.

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

 

From Bing Zhu, 2017-12-8 update

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