A Barcode Screen for Epigenetic Regulators Reveals a Role for the NuB4HAT-B Histone Acetyltransferase Complex in Histone Turnover 英文参考文献.docVIP
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A Barcode Screen for Epigenetic Regulators Reveals a Role for the NuB4HAT-B Histone Acetyltransferase Complex in Histone Turnover 英文参考文献
ABarcodeScreenforEpigeneticRegulatorsRevealsa
RolefortheNuB4/HAT-BHistoneAcetyltransferase
ComplexinHistoneTurnover
KittyF.Verzijlbergen1.,TiborvanWelsem1.,DaoudSie2,3,TinekeL.Lenstra4,DanielJ.Turner5¤,
FrankC.P.Holstege4,RonM.Kerkhoven2,3,FredvanLeeuwen1*
1Department of Gene Regulation, Netherlands Cancer Institute, Amsterdam, The Netherlands, 2Genome Center, Netherlands Cancer Institute, Amsterdam, The
Netherlands,3NetherlandsProteomicsCenter,Amsterdam,TheNetherlands,4DepartmentofMolecularCancerResearch,UniversityMedicalCenterUtrecht,Utrecht,The
Netherlands,5WellcomeTrustSangerInstitute,WellcomeTrustGenomeCampus,Hinxton,UnitedKingdom
Abstract
Dynamicmodificationofhistoneproteinsplaysakeyroleinregulatinggeneexpression.However,histonesthemselvescan
alsobedynamic,whichpotentiallyaffectsthestabilityofhistonemodifications.Todeterminethemolecularmechanismsof
histone turnover, we developed a parallel screening method for epigenetic regulators by analyzing chromatin states on
DNA barcodes. Histone turnover was quantified by employing a genetic pulse-chase technique called RITE, which was
combinedwithchromatinimmunoprecipitationandhigh-throughputsequencing.Inthisscreen,theNuB4/HAT-Bcomplex,
containingtheconservedtypeBhistoneacetyltransferaseHat1,wasfoundtopromotehistoneturnover.Unexpectedly,the
three members of this complex could be functionally separated from each other as well as from the known interacting
factorandhistonechaperoneAsf1.Thus,systematicanddirectinterrogationofchromatinstructureonDNAbarcodescan
leadtothediscoveryofgenesandpathwaysinvolvedinchromatinmodificationanddynamics.
Citation:VerzijlbergenKF,vanWelsemT,SieD,LenstraTL,TurnerDJ,etal.(2011)ABarcodeScreenforEpigeneticRegulatorsRevealsaRolefortheNuB4/HAT-B
HistoneAcetyltransferaseComplexinHistoneTurnover.PLoSGenet7(10):e1002284.doi:10.1371/journal.pgen.1002284
Editor:DirkSchu¨beler,FriedrichMiescherInstituteforBiomedicalResearch,Switzerland
ReceivedFebruary24,2011;AcceptedJuly29,2011;PublishedOctober6,20
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