Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation 英文参考文献.docVIP

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Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation 英文参考文献.doc

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Evidence of Influence of Genomic DNA Sequence on Human X Chromosome Inactivation 英文参考文献

EvidenceofInfluenceofGenomicDNASequence onHumanXChromosomeInactivation Zhong Wang, Huntington F.Willard, Sayan Mukherjee, Terrence S.Furey* InstituteforGenomeSciencesandPolicy,DukeUniversity,Durham,NorthCarolina,UnitedStatesofAmerica AsignificantnumberofhumanX-linkedgenesescapeXchromosomeinactivationandarethusexpressedfromboth the active and inactive X chromosomes. The basis for escape from inactivation and the potential role of the X chromosomeprimaryDNAsequenceindeterminingagene’sXinactivationstatusisunclear.Usingacombinationof theXchromosomesequenceandacomprehensiveXinactivationprofileofmorethan600genes,twoindependentyet complementaryapproacheswereusedtosystematicallyinvestigatetherelationshipbetweenXinactivationandDNA sequence features. First, statistical analyses revealed that a number of repeat features, including long interspersed nuclear element (LINE) and mammalian-wide interspersed repeat repetitive elements, are significantly enriched in regionssurroundingtranscriptionstartsitesofgenesthataresubjecttoinactivation,whileAlurepetitiveelementsand shortmotifscontainingACG/CGTaresignificantlyenrichedinthosethatescapeinactivation.Second,linearsupport vector machine classifiers constructed using primary DNA sequence features were used to correctly predict the X inactivationstatusfor.80%ofallX-linkedgenes.Wefurtheridentifiedasmallsetoffeaturesthatareimportantfor accurate classification, among which LINE-1 and LINE-2 content show the greatest individual discriminatory power. Finally, asfew as12 featurescan beused for accurate support vectormachine classification. Takentogether, these resultssuggestthatfeaturesoftheunderlyingprimaryDNAsequenceofthehumanXchromosomemayinfluencethe spreadingand/ormaintenanceofXinactivation. Citation:WangZ,WillardHF,MukherjeeS,FureyTS(2006)EvidenceofinfluenceofgenomicDNAsequenceonhumanXchromosomeinactivation.PLoSComputBiol2(9): e113.DOI:10.1371/journal.pcbi.0020113 The chromosome can be roughly divided into two regions [13–15]:anX-con