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1、NIHPublicAccessAuthorManuscriptAlcoholClinExpRes.Authormanuscript;availableinPMC2012April1.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptAlcoholClinExpRes.2011April;35(4):735±746.doi:10.1111/j.1530-0277.2010.01391.x.AlcoholaltersDNAMethylationPatte
2、rnsandInhibitsNeuralStemCellDifferentiationFengC.Zhou1,2,YokeshBalaraman1,7,MingXiangTeng3,4,5,8,YunlongLiu3,4,5,RobindraSingh1,andKennethP.Nephew61DepartmentofAnatomyandCellBiology,IndianaUniversitySchoolofMedicine,Indianapolis,IN46202,USA.2StarkNeuroscienceResearchInstitute,IndianaUniversitySch
3、oolofMedicine,Indianapolis,IN46202,USA.3DepartmentofMedicalandMolecularGenetics,IndianaUniversitySchoolofMedicine,Indianapolis,IN46202,USA.4CenterforComputationalBiologyandBioinformatics,IndianaUniversitySchoolofMedicine,Indianapolis,IN46202,USA.5CenterforMedicalGenomics,Indianapolis,IndianaUnive
4、rsitySchoolofMedicine,Indianapolis,IN46202,USA.6MedicalSciencesProgramandDepartmentofCellularIntegrativePhysiology,IndianaUniversitySchoolofMedicine,Indianapolis,IN46202,USA.7InstituteofPsychiatricResearch,IndianaUniversitySchoolofMedicine,Indianapolis,IN46202,USA.8SchoolofComputerScienceandTechn
5、ology,HarbinInstituteofTechnology,Harbin,Heilongjiang150001,PRChina.AbstractBackground—Potentialepigeneticmechanismsunderlyingfetalalcoholsyndrome(FAS)includealcohol-inducedalterationsofmethylmetabolism,resultinginaberrantpatternsofDNAmethylationandgeneexpressionduringdevelopment.Havingpreviously
6、demonstratedanessentialroleforepigeneticsinneuralstemcell(NSC)developmentandthatinhibitingDNAmethylationpreventsNSCdifferentiation,hereweinvestigatedtheeffectofalcoholexposureongenome-wideDNAmethylationpatternsandNSCdifferentiation.Methods—NSCsincultureweretreatedwithorwithouta6-hr88mM(“binge-lik
7、e”)alcoholexposureandexaminedat48hrs,formigration,growth,andgenome-wideDNAmethylation.TheDNAmethylationwasexaminedusingDNA-methylationimmunoprecipitation(MeDIP)followedbymicroarrayanalysis.Furthervalidationwasperformed
