Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition 英文参考文献.docVIP

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Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition 英文参考文献.doc

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Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition 英文参考文献

OverexpressionofTranscriptionFactorSp1Leadsto GeneExpressionPerturbationsandCellCycleInhibition EmmanuelleDeniaud1,2,3,Joe¨lBaguet1,2,3,RoxaneChalard1,2,3,BarizaBlanquier2,3,LiliaBrinza1,2,3 JulienMeunier1,2,3,Marie-Ce′cileMichallet1,2,3,Aure′lieLaugraud3,4,ClaudetteAh-Soon3,4 ,Anne , Wierinckx5,MarcCastellazzi2,3,6,Joe¨lLachuer5,ChristianGautier3,4,JacquelineMarvel1,2,3.* ,Yann Leverrier1,2,3. * 1Inserm, U851, Lyon, France, 2Universite′ Lyon1, IFR128, Lyon, France, 3Universite′ de Lyon, Lyon, France, 4PRABI, Villeurbanne, France, 5ProfileXpert, Bron, France, 6Inserm,U758,EcoleNormaleSupe′rieuredeLyon,Lyon,France Abstract Background:TheubiquitoustranscriptionfactorSp1regulatestheexpressionofavastnumberofgenesinvolvedinmany cellularfunctionsrangingfromdifferentiationtoproliferationandapoptosis.Sp1expressionlevelsshowadramaticincrease during transformation and this could play a critical role for tumour development or maintenance. Although Sp1 deregulation might be beneficial for tumour cells, its overexpression induces apoptosis of untransformed cells. Here we furthercharacterisedthefunctionalandtranscriptionalresponsesofuntransformedcellsfollowingSp1overexpression. MethodologyandPrincipalFindings:Wemadeuseofwild-typeandDNA-binding-deficientSp1todemonstratethatthe inductionofapoptosisbySp1isdependentonitscapacitytobindDNA.Genome-wideexpressionprofilingidentifiedgenes involved in cancer, cell death and cell cycle as being enriched among differentially expressed genes following Sp1 overexpression.InsilicosearchtodeterminethepresenceofSp1bindingsitesinthepromoterregionofmodulatedgenes wasconducted.GenesthatcontainedSp1bindingsitesintheirpromoterswereenrichedamongdown-regulatedgenes. The endogenous sp1 gene is one of the most down-regulated suggesting a negative feedback loop induced by overexpressed Sp1. In contrast, genes containing Sp1 binding sites in their promoters were not enriched among up- regulatedgenes.Theseresultssuggestthatthetranscriptionalresponseinvolves