INSIGHTSFROMGENOMICPROFILINGOFTRANSCRIPTIONFACTORSPeggyFarnhamDepartmentofPharmacologyandtheGenomeCenter,UniversityofCalifornia-Davis,Davis,CA,95616AbstractAcrucialquestioninthefieldofgeneregulationiswhetherthelocationatwhichatranscriptionfactorbindsinfluencesitseffectivenessorthemechanismbywhichitregulatestranscription.Comprehensivetranscriptionfactorbindingmapsareneededtoaddresstheseissues,andgenome-widemappingisnowpossiblethankstothetechnologicaladvancesofChIP-chipandChIP-Seq.Thisreviewdiscusseshowrecentgenomicprofilingoftranscriptionfactorsgivesinsightintohowbindingspecificityisachievedandwhatfeaturesofchromatininfluencetheabilityoftranscriptionfactorstointeractwiththegenome,andalsosuggestsfutureexperimentstofurtherourunderstandingofthecausesandconsequencesoftranscriptionfactor-genomeinteractions.IntroductionUnderstandinghowgenomicinformationistranslatedintogeneregulationhasbeenthesubjectofintensescientificinvestigationforthelastseveraldecades.Untilrecently,moststudiesfocusedondetailedcharacterizationofaparticulargeneorgenefamily.Thesestudiesresultedinthedevelopmentofgeneralprinciplesofgeneregulation,butgenome-scalestudiesarenowpromptingre-examinationofsomeoftheseprinciples.Theestablishedviewoftranscriptionalregulationisthatcisregulatoryelements,suchaspromotersandenhancers,andproteinsthatbindtotheseelementscontroldifferentlevelsoftranscriptionofdifferentgenes1,2.Promotersarecomposedofcommonsequenceelements,suchasaTATAboxandinitiator,andbindingsitesforothertranscriptionfactors,whichworktogethertorecruitthegeneraltranscriptionalmachinerytothetranscriptionalstartsite(TSS).Enhancersalsocontainbindingsitesfortranscriptionfactorsbutarelocatedsomedistancefromthesiteoftranscriptioninitiation.Transcriptionalactivityresultingfromthegeneralfactorsbindingtothecorepromoterisusuallyquitelowbutcanbeincreasedbysite-specificfactorsbindingtoproximalpromoterregions,whichcanhelptorecruitorstabilizetheinteractionofthegeneralfactorsatthecorepromoter.Promoteractivitycanbefurthersti...
