Genomic Sequence Is Highly Predictive of Local Nucleosome Depletion 英文参考文献.docVIP

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Genomic Sequence Is Highly Predictive of Local Nucleosome Depletion 英文参考文献.doc

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Genomic Sequence Is Highly Predictive of Local Nucleosome Depletion 英文参考文献

GenomicSequenceIsHighlyPredictive ofLocalNucleosomeDepletion Guo-Cheng Yuan1,2,*,Jun S.Liu1,3,* 1DepartmentofBiostatistics,HarvardSchoolofPublicHealth,Boston,Massachusetts,UnitedStatesofAmerica,2DepartmentofBiostatisticsandComputationalBiology, Dana-FarberCancerInstitute,Boston,Massachusetts,UnitedStatesofAmerica,3DepartmentofStatistics,HarvardUniversity,Cambridge,Massachusetts,UnitedStatesof America The regulation of DNA accessibility through nucleosome positioning is important for transcription control. Computational models have been developed to predict genome-wide nucleosome positions from DNA sequences, butthesemodelsconsideronlynucleosomesequences,whichmayhavelimitedtheirpower.Wedevelopedastatistical multi-resolutionapproachtoidentifyasequencesignature,calledtheN-score,thatdistinguishesnucleosomebinding DNAfromnon-nucleosomeDNA.Thisnewapproachhassignificantlyimprovedthepredictionaccuracy.Thesequence information is highly predictive for local nucleosome enrichment or depletion, whereas predictions of the exact positionsareonlymodestlymoreaccuratethananullmodel,suggestingtheimportanceofotherregulatoryfactorsin fine-tuningthenucleosomepositions.TheN-scoreinpromoterregionsisnegativelycorrelatedwithgeneexpression levels.RegulatoryelementsareenrichedinlowN-scoreregions.Whileourmodelisderivedfromyeastdata,theN- scorepatterncomputedfromthismodelagreeswellwithrecenthigh-resolutionprotein-bindingdatainhuman. Citation:YuanG-C,LiuJS(2008)Genomicsequenceishighlypredictiveoflocalnucleosomedepletion.PLoSComputBiol4(1):e13.doi:10.1371/journal.pcbi.0040013 positionsalsohelpsdownstreamfunctionalanalyses,suchas improving prediction accuracies of transcription factor Introduction In eukaryotic cells, nucleosomes play important roles in diversebiologicalprocesses,including transcriptioncontrol, DNAreplicationandrepair[1].Thepositionsofnucleosomes mustbewell-coordinated inordertoensurepropercontrol oftheseactivities.Thecoordinationofnucleosomepositions is a complex process inv