Sex-specific mouse liver gene expression genome-wide analysis of developmental changes from pre-pubertal period to young adulthood 英文参考文献.docVIP

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Sex-specific mouse liver gene expression genome-wide analysis of developmental changes from pre-pubertal period to young adulthood 英文参考文献.doc

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Sex-specific mouse liver gene expression genome-wide analysis of developmental changes from pre-pubertal period to young adulthood 英文参考文献

ConfortoandWaxmanBiologyofSexDifferences2012,3:9 /content/3/1/9 RESEARCH OpenAccess Sex-specificmouselivergeneexpression: genome-wideanalysisofdevelopmentalchanges frompre-pubertalperiodtoyoungadulthood TaraLConfortoandDavidJWaxman* Abstract Background:Earlyliverdevelopmentandthetranscriptionaltransitionsduringhepatogenesisarewell characterized.However,geneexpressionchangesduringthelatepostnatal/pre-pubertaltoyoungadulthood periodarelesswellunderstood,especiallywithregardstosex-specificgeneexpression. Methods:Microarrayanalysisofmaleandfemalemouseliverwascarriedoutat3,4,and8wkofagetoelucidate developmentalchangesingeneexpressionfromthelatepostnatal/pre-pubertalperiodtoyoungadulthood. Results:Alargenumberofsex-biasedandsex-independentgenesshowedsignificantchangesduringthis developmentalperiod.Notably,sex-independentgenesinvolvedincellcycle,chromosomecondensation,and DNAreplicationweredownregulatedfrom3wkto8wk,whilegenesassociatedwithmetalionbinding,ion transportandkinaseactivitywereupregulated.Amajorityofgenesshowingsexdifferentialexpressioninadult liverdidnotdisplaysexdifferencespriortopuberty,atwhichtimeextensivechangesinsex-specificgene expressionwereseen,primarilyinmales.Thus,inmaleliver,76%ofmale-specificgeneswereupregulatedand 47%offemale-specificgenesweredownregulatedfrom3to8wkofage,whereasinfemaleliver67%ofsex- specificgenesshowednosignificantchangeinexpression.Inbothsexes,genesupregulatedfrom3to8wkwere significantlyenriched(pE-76)inthesetofgenespositivelyregulatedbythelivertranscriptionfactorHNF4a ,as determinedinaliver-specificHNF4aknockoutmousemodel,whilegenesdownregulatedduringthis developmentalperiodshowedsignificantenrichment(pE-65)fornegativeregulationbyHNF4a .Significant enrichmentofthedevelopmentallyregulatedgenesinthesetofgenessubjecttopositiveandnegativeregulation bypituitaryhormonewasalsoobserved.Fivesex-specifictranscriptionalregulatorsshowedsex-specificexpression at4wk(male-specificIhh;female-specificCdx4,Cux2,Tox,andTrim24)andmaycontributetot