Absenceofasimplecode:howtranscriptionfactorsreadthegenomeMatthewSlattery1,2,*,TianyinZhou3,#,LinYang3,#,AnaCarolinaDantasMachado3,#,RalucaGordân4,*,andRemoRohs3,*1DepartmentofBiomedicalSciences,UniversityofMinnesotaMedicalSchool,Duluth,MN55812,USA2DevelopmentalBiologyCenter,UniversityofMinnesota,Minneapolis,MN55455,USA3MolecularandComputationalBiologyProgram,DepartmentsofBiologicalSciences,Chemistry,Physics,andComputerScience,UniversityofSouthernCalifornia,LosAngeles,CA90089,USA4CenterforGenomicandComputationalBiology,DepartmentsofBiostatisticsandBioinformatics,ComputerScience,andMolecularGeneticsandMicrobiology,DukeUniversity,Durham,NC27708,USAAbstractTranscriptionfactors(TFs)influencecellfatebyinterpretingtheregulatoryDNAwithinagenome.TFsrecognizeDNAinaspecificmanner;themechanismsunderlyingthisspecificityhavebeenidentifiedformanyTFs,basedonthree-dimensionalstructuresofprotein-DNAcomplexes.Morerecently,structuralviewshavebeencomplementedwithdatafromhigh-throughputinvitroandinvivoexplorationsoftheDNAbindingpreferencesofmanyTFs.Together,theseapproacheshavegreatlyexpandedourunderstandingofTF-DNAinteractions.However,themechanismsbywhichTFsselectinvivobindingsitesandaltergeneexpressionremainunclear.RecentworkhashighlightedthemanyvariablesthatinfluenceTF-DNAbinding,whiledemonstratingthatabiophysicalunderstandingofthesemanyfactorswillbecentraltounderstandingTFfunction.Keywordstranscriptionfactor;TF-DNAbindingspecificity;high-throughputbindingassays;quantitativemodeling;cooperativeTFbinding;chromatinaccessibility©2014ElsevierLtd.Allrightsreserved.Correspondingauthors:Rohs,R.(rohs@usc.edu),Slattery,M.(mslatter@umn.edu),andGordân,R.(raluca.gordan@duke.edu).#Theseauthorscontributedequally.Publisher'sDisclaimer:ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript.Themanuscriptwillundergocopyediting,typesetting,andreviewoftheresultingproofbeforeitispublishedinitsfinalcitableform.Pleasen...
