AssociateInvestigator,NIBS,Beijing,ChinaPhone：010-80726688
Fax：010-80726689
E-mail：zhubing@nibs.ac.cn
GroupWebsite:http://zhulab.nibs.ac.cn
教育经历Education1999年中国科学院上海植物生理研究所分子遗传学博士Ph.D.,ShanghaiInstituteofPlantPhysiology,ChineseAcademyofSciences1995年中国水稻研究所遗传学硕士M.S.,ChinaNationalRiceResearchInstitute1992年浙江大学生物科学与技术系学士B.S.,ZhejiangUniversity,China工作经历ProfessionalExperience2011年-北京生命科学研究所高级研究员AssociateInvestigator,NationalInstituteofBiologicalSciences,Beijing,China2006-2011年北京生命科学研究所研究员AssistantInvestigator,NationalInstituteofBiologicalSciences,Beijing,China2002-2006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，DannyReinberg博士实验室博士后ResearchTeachingSpecialist,LabofDr.DannyReinberg,Howard-HughesMedicalInstitute/UniversityofMedicineandDentistryofNewJersey/RobertWoodJohnsonMedicalSchool1999-2002年瑞士弗雷德里克-米歇尔研究所，Jean-PierreJost博士实验室博士后ResearchFellow,LabofDr.Jean-PierreJost,FriedrichMiescherInstitute,Switzerland研究概述ResearchDescription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:plasticityversusinheritabilityDNAisunarguablythecarrierofgeneticinformation.However,DNAsequencealonecannotexplainhowhundredsofcelltypesinacomplexmulti-cellularorganism,suchasahumanindividualcanpossessdistincttranscriptionprograms,whilesharingthesamegeneticinformation.Thisisbelievedtobeachievedbyfine-tuningourgeneticinformationwithaso-called“epigenetic”system.Epigeneticsystemmustsimultaneouslyofferdualcharacteristics,“Plasticity&Inheritability”.Plasticityallowsthetransformationofonegenomeintohundredsofepigenomesandtranscriptomes,whereasinheritabilitypermitsthemaintenanceofeverysingleepigenomeanditscorrespondingtranscriptome.Ourresearchfocusonthefollowingfields:1.EstablishmentandmaintenanceofepigeneticinformationSeveralhistonemodificationsandDNAmethylationhavebeenshowntobecriticalinclassicepigeneticphenomena,includingPositioneffectvariegation,Polycombsilencing,dosagecompensationandimprinting.Usingcombinatoryapproachesbyintegratingbiochemistry,quantitativemassspectrometry,high-throughputsequencingandunbiasedscreening,weattempttoidentifyandtomechanisticallyunderstandregulatorymechanismscriticalfortheestablishmentandmaintenanceofepigeneticinformation.2.EnzymaticactivityregulationofchromatinmodifyingenzymesAnotherimportantdirectioninourlaboratoryistostudythebiochemicalregulationofchromatinmodifyingenzymes.Despitetheexponentiallyincreasingnumberofstudiesaboutchromatinmodifyingenzymes,themechanisticregulationoftheseenzymesispoorlyunderstood.Therefore,weareinterestedinunderstandingthemolecularmechanismsbehindactivationandantagonizationofchromatinmodifyingenzymes.Webelievethisisanimportantdirectionforchromatinbiology,notonlybecauseofmechanisticinsightsthatcanbederivedfromsuchstudies,butalsobecauseamechanisticunderstandingwillcontributetoguidedsmallmoleculeinhibitordesignforchromatinmodifyingenzymes.Thisgoalisparticularlyimportantbecausemanychromatinmodifyingenzymes,suchashistonedeacetylases(HDACs)and,morerecently,PRC2,arebeingconsideredaspotentialdrugtargets.Researchpublications1.HuangC,ZhangZ,XuX,LiY,LiZ,MaY,CaiT,ZhuB.H3.3-H4tetramersplittingeventsfeaturecell-typespecificenhancers.PlosGenet.2013;9:e10035582.YangN,WangW,WangY,WangM,ZhaoQ,RaoZ,ZhuB,XuRM.Distinctmodeofmethylatedlysine-4ofhistoneH3recognitionbytandemtudor-likedomainsofSpindlin1.ProcNatlAcadSciUSA.2012;109:179543.YuanW,WuT,FuH,DaiC,WuH,LiuN,LiX,XuM,ZhangZ,NiuT,HanZ,ChaiJ,ZhouXJ,GaoS,ZhuB.DensechromatinactivatesPolycombrepressivecomplex2toregulateH3Lysine27methylation.Science2012;337:9714.XuM,ChenS,ZhuB.Investigatingthecellcycle-associateddynamicsofhistonemodificationsusingquantitativemassspectrometry.MethodEnzymol.2012;512:295.XuM,WangW,ChenS,ZhuB.Amodelformitoticinheritanceofhistonelysinemethylation.EMBORep.2012;13:606.WangW,MaoZ,ZhangH,DingX,ChenS,ZhangX,ZhuB.NucleolarproteinSpindlin1recognizesH3K4me3andfacilitatesrRNAgenetranscription.EMBORep.2011;12:11607.YangP,WangY,ChenJ,LiH,KangL,ZhangY,ChenS,ZhuB,GaoS.RCOR2isasubunitoftheLSD1complexthatregulatesEScellpropertyandsubstitutesforSOX2inreprogrammingsomaticcellstopluripotency.StemCells2011;29:7918.ChenX,XiongJ,XuM,ChenS,ZhuB.Symmetricmodificationwithinanucleosomeisnotgloballyrequiredforhistonelysinemethylation.EMBORep.2011;12:2449.YuanW,XuM,HuangC,LiuN,ChenS,ZhuB.H3K36methylationantagonizesPRC2mediatedH3K27methylation.JBiolChem.2011;286:798310.WuH,ChenX,XiongJ,LiY,LiH,DingX,LiuS,ChenS,GaoS,ZhuB.HistonemethyltransferaseG9acontributestoH3K27methylationinvivo.CellRes.2011;21:36511.XuM,LongC,ChenX,HuangC,ChenS,ZhuB.PartitionofhistoneH3-H4tetramersduringDNAreplication-dependentchromatinassembly.Science2010;328:9412.JiaG,WangW,LiH,MaoZ,CaiG,SunJ,WuH,XuM,YangP,YuanW,ChenS,ZhuB.Asystematicevaluationofthecompatibilityofhistonescontainingmethyl-lysineanalogueswithbiochemicalreactions.CellRes.2009;19:121713.YuanW,XieJ,LongC,Erdjument-BromageH,DingX,ZhengY,TempstP,ChenS,ZhuB,ReinbergD.HeterogeneousnuclearribonucleoproteinLIsasubunitofhumanKMT3a/Set2complexrequiredforH3Lys-36trimethylationactivityinvivo.JBiolChem.2009;284:1570114.MoniauxN,NemosC,DebS,ZhuB,DornreiterI,HollingsworthMA,BatraSK(2009)ThehumanRNApolymeraseII-associatedfactor1(hPaf1):anewregulatorofcell-cycleprogression.PLoSOne4:e707715.PavriR,ZhuB,LiG,TrojerP,MandalS,ShilatifardA,ReinbergD.HistoneH2BmonoubiquitinationfunctionscooperativelywithFACTtoregulateelongationbyRNApolymeraseII.Cell2006;125:70316.AdelmanK,WeiW,ArdehaliMB,WernerJ,ZhuB,ReinbergD,LisJT.DrosophilaPaf1modulateschromatinstructureatactivelytranscribedgenes.MolCellBiol.2006;26:25017.ZhuB,ZhengY,PhamAD,MandalSS,Erdjument-BromageH,TempstP,ReinbergD.MonoubiquitinationofhumanhistoneH2B:thefactorsinvolvedandtheirrolesinHOXgeneregulation.MolCell2005;20:60118.ZhuB,MandalSS,PhamAD,ZhengY,Erdjument-BromageH,BatraSK,TempstP,ReinbergD.ThehumanPAFcomplexcoordinatestranscriptionwitheventsdownstreamofRNAsynthesis.GenesDev.2005;19:166819.JostJP,OakeleyEJ,ZhuB,BenjaminD,ThiryS,SiegmannM,JostYC.5-MethylcytosineDNAglycosylaseparticipatesinthegenome-widelossofDNAmethylationoccurringduringmousemyoblastdifferentiation.NucleicAcidsRes.2001;29:445220.ZhuB,BenjaminD,ZhengY,AnglikerH,ThiryS,SiegmannM,JostJP.Overexpressionof5-methylcytosineDNAglycosylaseinhumanembryonickidneycellsEcR293demethylatesthepromoterofahormone-regulatedreportergene.ProcNatlAcadSciUSA.2001;98:503121.ZhuB,ZhengY,AnglikerH,SchwarzS,ThiryS,SiegmannM,JostJP.5-MethylcytosineDNAglycosylaseactivityisalsopresentinthehumanMBD4(G/Tmismatchglycosylase)andinarelatedaviansequence.NucleicAcidsRes.2000;28:415722.ZhuB,ZhengY,HessD,AnglikerH,SchwarzS,SiegmannM,ThiryS,JostJP.5-methylcytosine-DNAglycosylaseactivityispresentinaclonedG/TmismatchDNAglycosylaseassociatedwiththechickenembryoDNAdemethylationcomplex.ProcNatlAcadSciUSA.2000;97:5135Invitedreviews1.HuangC,XuM,ZhuB.Epigeneticinheritancemediatedbyhistonelysinemethylation:maintainingtranscriptionalstateswithoutthepreciserestorationofmarks?PhilosTransRSocLondBBiolSci.2013;368:20110332.2.TalbertPB,AhmadK,AlmouzniG,AusióJ,BergerF,BhallaPL,BonnerWM,CandeWZ,ChadwickBP,ChanSW,CrossGA,CuiL,DimitrovSI,DoeneckeD,Eirin-LópezJM,GorovskyMA,HakeSB,HamkaloBA,HolecS,JacobsenSE,KamieniarzK,KhochbinS,LadurnerAG,LandsmanD,LathamJA,LoppinB,MalikHS,MarzluffWF,PehrsonJR,PostbergJ,SchneiderR,SinghMB,SmithMM,ThompsonE,Torres-PadillaME,TremethickDJ,TurnerBM,WaterborgJH,WollmannH,YelagandulaR,ZhuB,HenikoffS.Aunifiedphylogeny-basednomenclatureforhistonevariants.EpigenetChromatin2012;5:73.YuanG,ZhuB.Histonevariantsandepigeneticinheritance.BBA-GeneRegulMech.2012;1819:2224.ZhuB,ReinbergD.Epigeneticsinheritance:Uncontested?CellRes.2011;21:4355.WuH,ZhuB.Splitdecision:whyitmatters?FrontBiol.2011;6:886.XuM,ZhuB.Nucleosomeassemblyandepigeneticinheritance.ProteinCell2010;1:820
