Identification of Conserved Regulatory Elements in Mammalian Promoter Regions: A Case Study Using the PCK1 Promoter

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    摘要 Asystematicphylogeneticfootprintingapproachwasperformedtoidentifycon-servedtranscriptionfactorbindingsites(TFBSs)inmammalianpromoterregionsusinghuman,mouseandratsequencealignments.Wefoundthatthescoredis-tributionsofmostbindingsitemodelsdidnotfollowtheGaussiandistributionrequiredbymanystatisticalmethods.Therefore,weperformedanempiricaltesttoestablishtheoptimalthresholdforeachmodel.WegaugedourcomputationalpredictionsbycomparingwithpreviouslyknownTFBSsinthePCK1genepro-moterofthecytosolicisoformofphosphoenolpyruvatecarboxykinase,andachievedasensitivityof75%andaspecificityofapproximately32%.Almostallknownsitesoverlappedwithpredictedsites,andseveralnewputativeTFBSswerealsoidentified.WevalidatedapredictedSP1bindingsiteinthecontrolofPCK1tran-scriptionusinggelshiftandreporterassays.Finally,weappliedourcomputationalapproachtothepredictionofputativeTFBSswithinthepromoterregionsofallavailableRefSeqgenes.OurfullsetofTFBSpredictionsisfreelyavailableathttp://bfgl.anri.barc.usda.gov/tfbsConsSites.
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    出版日期 2008年03月13日(中国Betway体育网页登陆平台首次上网日期,不代表论文的发表时间)
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