Domain Requirements and Sequence Specificity of DNA Binding for the Forkhead Transcription Factor FOXP3 英文参考文献.docVIP
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Domain Requirements and Sequence Specificity of DNA Binding for the Forkhead Transcription Factor FOXP3 英文参考文献
DomainRequirementsandSequenceSpecificityofDNA
BindingfortheForkheadTranscriptionFactorFOXP3
KianPengKoh.,MarkS.Sundrud.¤,AnjanaRao*
DepartmentofPathology,HarvardMedicalSchoolandImmuneDiseaseInstitute,Boston,Massachusetts,UnitedStatesofAmerica
Abstract
Theforkhead,winged-helixtranscriptionfactorFOXP3ispreferentiallyexpressedinTregulatory(Treg)cellsandiscriticalfor
their immunosuppressive function. Mutations that abolish FOXP3 function lead to systemic autoimmunity in mice and
humans.However,themannerbywhichFOXP3recognizescognateDNAelementsisunclear.Hereweidentifyaninvitro
optimized DNA sequence to assess FOXP3 DNA binding by electrophoretic mobility shift assay (EMSA). The optimized
sequencecontainstwotandemcopiesofacoreDNAelementresembling,butnotidenticalto,thecanonicalforkhead(FKH)
binding element. The tandem nature of this optimized FOXP3-binding oligonucleotide suggests a requirement for
multimerization, and EMSA experiments confirm that both the DNA-binding FKH domain and an intact leucine-zipper
domain,whichmediateshomo-multimerizationofFOXP3,arerequiredforDNAbinding.Theseresultsestablishapractical
framework for understanding the molecular basis by which FOXP3 regulates gene transcription and programs Treg
suppressivefunction.
Citation:KohKP,SundrudMS,RaoA(2009)DomainRequirementsandSequenceSpecificityofDNABindingfortheForkheadTranscriptionFactorFOXP3.PLoS
ONE4(12):e8109.doi:10.1371/journal.pone.0008109
Editor:DeryaUnutmaz,NewYorkUniversitySchoolofMedicine,UnitedStatesofAmerica
ReceivedOctober19,2009;AcceptedNovember3,2009;PublishedDecember1,2009
Copyright:?2009Kohetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted
use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisworkwasfundedbyNIHgrantstoA.R.(ROIAI48213andR37CA42471).M.S.SwassupportedbytheIrvingtonInstitutefellowshipprogramofthe
CancerResearchInstitute.Thefundershadnoroleinstudydesign,datac
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