Members of the HNF-3/forkhead Family of Transcription Factors Exhibit Distinct Cellular Expression Patterns in Lung and Regulate the Surfactant Protein B Promoter

[摘要] Thehepatocytenuclearfactor3(HNF-3)/forkhead(fkh)proteinsconsistofanextensivefamilyoftissue-specificanddevelopmentalgeneregulatorswhichsharehomologywithinthewingedhelixDNAbindingmotif.Wereportontheisolationofanewfamilymember,HNF-3/forkheadhomolog8(HFH-8),fromlungcDNAlibrariesandthederivationofthecompleteaminoacidsequencesfortheHFH-8proteinaswellaspreviouslyidentifiedHFH-1andHFH-4proteins.TheHFHproteinscontainseveralsequencemotifsfoundinactivationdomainsofothertranscriptionfactorsandHNF-3/fkhfamilymembers.InsituhybridizationwiththeHNF-3,HFH-4,andHFH-8probesinadultlungdemonstratethattheHNF-3/fkhcellularexpressionpatternsareregionallyspecified.WhereasHNF-3αandHNF-3βarenormallycoexpressedinthehepatocyte,theirexpressionpatternsinthelungaredifferent.TheHNF-3αandHFH-4genesarecoexpressedinthebronchiolarepithelium(claracells),whereastheHNF-3βprobeexhibitsprominenthybridizationwiththesmoothmusclesurroundingarteriolesandbronchioles.Incontrast,HFH-8probeslabeledthetypeIIpneumocytecellsliningtherespiratorysurfacesofterminalbronchiolesandalveolarsac.WehaveidentifiedanHNF-3consensusDNAbindingsequenceintheproximalsurfactantproteinB(SPB)promoterregion(SPB-f2,-78to-88).SPBgenetranscriptionisrestrictedtobronchiolarandalveolarepitheliumwhichcolocalizeswiththeexpressionpatternoftheHNF-3αandHFH-8genes,respectively.WeshowthattheSPB-f2sequenceisrecognizedbybothHNF-3αandHFH-8proteinsandthatthesecDNAexpressionvectorsactivatetheSPBpromoterincotransfectionassaysthroughtheHNF-3consensussequence.OurresultssuggestthatSPBpromoteractivityisregulatedbyHNF-3αandHFH-8proteinsinacelltype-specificmanner.