朱冰博士 - 科学研究 - 北京生命科学研究所

朱冰博士

北京生命科学研究所高级研究员

Bing Zhu, Ph.D. Associate Investigator, NIBS, Beijing, China

Phone：010-80726688

Fax： 010-80726689

E-mail：zhubing@nibs.ac.cn

教育经历

Education

1999年中国科学院上海植物生理研究所分子遗传学博士

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

1995年中国水稻研究所遗传学硕士

M.S., China National Rice Research Institute

1992年浙江大学生物科学与技术系学士

B.S., Zhejiang University, China

工作经历

Professional Experience

2011-2015年北京生命科学研究所高级研究员

Associate Investigator, National Institute of Biological Sciences, Beijing, China

2006- 2011年北京生命科学研究所研究员

Assistant Investigator, National Institute of Biological Sciences, Beijing, China

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

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

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

研究概述

Research Description

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。

Epigenetics: plasticity versus inheritability

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. 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. Our research focus on the following fields:

1.Establishment and maintenance of epigenetic information

Several histone modifications and DNA methylation have been shown to be critical in classic epigenetic phenomena, including Position effect variegation, Polycomb silencing, dosage compensation and imprinting. Using combinatory approaches by integrating biochemistry, quantitative mass spectrometry, high-throughput sequencing and unbiased screening, we attempt to identify and to mechanistically understand regulatory mechanisms critical for the establishment and maintenance of epigenetic information.

2.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

1. 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

2. 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

3. 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

4. Xu M, Chen S, Zhu B. Investigating the cell cycle-associated dynamics of histone modifications using quantitative mass spectrometry. Method Enzymol. 2012; 512: 29

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

6. Wang W, Mao Z, Zhang H, Ding X, Chen S, Zhang X, Zhu B. Nucleolar protein Spindlin1 recognizes H3K4me3 and facilitates rRNA gene transcription. EMBO Rep. 2011; 12: 1160

7. 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 ES cell property and substitutes for SOX2 in reprogramming somatic cells to pluripotency. Stem Cells 2011; 29: 791

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

Invited reviews

1. 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.

2. 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

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

4. Zhu B, Reinberg D. Epigenetics inheritance: Uncontested? Cell Res. 2011; 21: 435

5. Wu H, Zhu B. Split decision: why it matters? Front Biol. 2011; 6: 88

6. Xu M, Zhu B. Nucleosome assembly and epigenetic inheritance. Protein Cell2010; 1: 820