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
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
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.
1. 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
2. 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
3. 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
4. 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
5. Xu M, Chen S, Zhu B. Investigating the cell cycle-associated dynamics of histone modifications using quantitative mass spectrometry. Method Enzymol. 2012; 512: 29
6. Xu M, Wang W, Chen S, Zhu B. A model for mitotic inheritance of histone lysine methylation. EMBO Rep. 2012; 13: 60
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
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