1992 - B.S., Zhejiang University, China

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

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

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

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

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

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

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

1. Epigenetics: plasticity versus inheritability

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.

2. 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.

3. 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. Ge W, Yu C, Li J, Yu Z, Li X, Zhang Y, Liu CP, Li Y, Tian C, Zhang X, Li G,Zhu B*, Xu RM*. Basis of the H2AK119 specificity of the Polycomb repressive deubiquitinase.Nature. 2023; 616: 176-182.

2. Shan Z, Zhang Y, Bu J, Li H, Zhang Z, Xiong J*,Zhu B*. The patterns and participants of parental histone recycling during DNA replication in Saccharomyces cerevisiae.Sci China Life Sci. 2023 Mar 9. Online ahead of print.

3. Sun J, Liu F, Yuan L, Pang NN,Zhu B, Yang N*. Mechanism studies of the activation of DNA methyltransferase DNMT1 triggered by histone H3 ubiquitination, revealed by multi-scale molecular dynamics simulations.Sci China Life Sci. 2023; 66: 313-323.

4. Zhang J, Zhang Y, You Q, Huang C, Zhang T, Wang M, Zhang T, Yang X, Xiong J, Li Y, Liu CP, Zhang Z, Xu RM*,Zhu B*. Highly enriched BEND3 prevents the premature activation of bivalent genes during differentiation.Science. 2022; 375: 1053-1058.

5. Ming X,Zhu B, Zhang Z*. Simultaneously measuring the methylation of parent and daughter strands of replicated DNA at the single-molecule level by Hammer-seq.Nat Protoc. 2021; 16: 2131-2157.

6. Dai L, Xiao X, Pan L, Shi L, Xu N, Zhang Z, Feng X, Ma L, Dou S, Wang P,Zhu B, Li W, Zhou Z*. Recognition of the inherently unstable H2A nucleosome by Swc2 is a major determinant for unidirectional H2A.Z exchange.Cell Rep. 2021; 35: 109183.

7. Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Bi X, Shao W, Hong Y, Wu Z, Ma R, Wang P, Li W, Zhang J, Chang Z, Hou Y,Zhu B, Ramalho-Santos M, Li P, Xie W, Na J, Sun Y, Shen X. Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome.Cell Res. 2021; 31: 613-630.

8. Zhao Z, Zhang Z, Li J, Dong Q, Xiong J, Li Y, Lan M, Li G,Zhu B*. Sustained TNF-α stimulation induces transcriptional memory that greatly enhances signal sensitivity and robustness.eLife. 2020; 9: e61965.

9. Wang Q, Yu G, Ming X, Xia W, Xu X, Zhang Y, Zhang W, Li Y, Huang C, Xie H,Zhu B*, Xie W*. Imprecise DNMT1 activity coupled with neighbor-guided correction enables robust yet flexible epigenetic inheritance.Nat Genet. 2020; 52: 828-839.

10. 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; 30: 980-996.

11. 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.

12. 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.

13. 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; 14:1103-1118.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

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

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.

51. 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.

52. 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.

53.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.

54.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.

55. 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.

56.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.

57.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.

58.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.