ReviewTranscriptionFactorsandDNAPlayHideandSeekDavidM.Suter1,*Transcriptionfactors(TFs)bindtospecificDNAmotifstoregulatetheexpressionoftargetgenes.Toreachtheirbindingsites,TFsdiffusein3Dandperformlocalmotionssuchas1Dsliding,hopping,orintersegmentaltransfer.TF–DNAinter-actionsdependonmultipleparameters,suchasthechromatinenvironment,TFpartitioningintodistinctsubcellularregions,andcooperativitywithotherDNA-bindingproteins.Inthisreview,howcurrentunderstandingofthesearchprocesshasinitiallybeenshapedbyprokaryoticstudiesisdiscussed,aswellaswhatisknownabouttheparametersregulatingTFsearchefficiencyinthecontextofthecomplexeukaryoticchromatinlandscape.TranscriptionFactorsAreUniversalMasterRegulatorsofGeneExpressionGeneexpressioniscentraltoalllivingsystemsandsubjecttoacomplexregulationallthewayfromRNAsynthesistoproteindegradation.TranscriptionalinitiationisthemostimportantpointofcontrolinthegeneexpressioncascadeandisregulatedbytwoclassesofDNA-interactingpro-teins:(i)gene-nonspecificfactors,suchasRNApolymeraseII,generaltranscriptionfactors,andenzymesinvolvedinhistonemodificationsandDNAmethylation;and(ii)gene-specificfactors,alsocommonlycalled‘transcriptionfactors’(TFs)[1].Gene-nonspecificfactorscannotbythem-selvesdeterminewhichgenestoregulateinaparticularcontext.Bycontrast,TFsarecharacter-izedbytheirsequencespecificity,whichallowsthemtoactivateorrepresstranscriptionoftargetgenes[1].Inprokaryotes,mostTFsactasinhibitorsoftranscriptionbystericallyhinderingtheprogressionofRNApolymerase.Theydosobybindingtoasmallnumberofgenomiclocationstoregulateveryspecificaspectsofbacteriallife,suchaslactosemetabolismorbiosynthesisoftryptophan[2].Bycontrast,eukaryoticTFshavedevelopedanarsenalofmolecularmechanismstodealwiththecomplexbiochemicalenvironmentofeukaryoticchromatin.Thisisachievedthroughspecificdomainsallowingrecruitmentofnon–sequence-specificregulatorsthatimpacttranscriptionatdifferentlevels,suchasDNAaccessibilityorrecruitmentoftheRNApolymeraseIImachinery[1].Despiteverydifferentmode...
