Transcriptionfactors:specificDNAbindingandspecificgeneregulationAnne-LaureTodeschini1,2,AdrienGeorges1,2,andReinerA.Veitia1,21InstitutJacquesMonod,Paris,France2Universite´ParisDiderot,Paris,FranceSpecificrecognitionofcis-regulatoryregionsisessentialforcorrectgeneregulationinresponsetodevelopmentalandenvironmentalsignals.SuchDNAsequencesarerecognizedbytranscriptionfactors(TFs)thatrecruitthetranscriptionalmachinery.Achievementofspecificsequencerecognitionisnotatrivialproblem;manyTFsrecognizesimilarconsensusDNA-bindingsitesandagenomecanharborthousandsofconsensusornear-consensussequences,bothfunctionalandnonfunction-al.Althoughgenomictechnologieshaveprovidedlarge-scalesnapshotsofTFbinding,afullunderstandingofthemechanisticandquantitativedetailsofspecificrecogni-tioninthecontextofgeneregulationislacking.Here,weexplorethevariouswaysinwhichTFsrecognizingsimi-larconsensussitesdistinguishtheirowntargetsfromalargenumberofothersequencestoensurespecificcellularresponses.SpecificrecognitionofDNA-bindingsitesandspecifictranscriptionalresponses:nontrivialproblemsThespecificityoftranscriptionregulationinallorganismsdependsontheabilityofTFs,thetranselementsofthegeneexpressionsystem,tointeractwithcis-regulatoryregions(CRRs)ofDNA.Aproductivetranscriptionreac-tioncantakeplaceonlyifalltherequired(cisandtrans)factors‘cooperate’torecruitthetranscriptionalmachin-ery[1].Prokaryotesandeukaryotesusedifferentstrate-giestotargetTFstospecificgenomelocations.BacterialTFstendtorecognizeextendedDNAsites,whichisenoughtoensurespecificityinsmallgenomes.Bycon-trast,eukaryoticTFstypicallyrecognizeshortersequencesandthereforeclusteringofsitesisoftenre-quiredtoachievespecificrecognition[2].Inaddition,theseshortermotifscanoccurmanytimesinlargeeukaryoticgenomes,andTFsdisplaywidespread,nonfunctionalbinding.TFconsensusbindingsitescanbedeterminedeitherinvitrothroughaprocess(oftencalledSelex)ofselectiveenrichmentstartingfromrandomdouble-stranded(ds)DNAoligonucleotidesequences[3,4]orinvivothroughtheidentif...
