AP‐1 protein induction during monopoiesis favors C/EBP: AP‐1 heterodimers over C/EBP homodimerization and stimulates FosB transcription

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: c‐;    Jun;    c‐;    Fos;    myeloid;    leucine zipper;   

DOI  :  10.1189/jlb.0111043

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AP‐1proteinsheterodimerizeviatheirLZdomainstobindTGACGTCAorTGACTCA,whereasC/EBPsdimerizetobindATTGCGCAAT.WedemonstratethatintactC/EBPαalsoheterodimerizeswithc‐Junorc‐FostobindahybridDNAelement,TGACGCAA,ormoreweaklytoTGATGCAA.A2:1ratioofc‐Jun:C/EBPαorc‐Fos:C/EBPαwassufficientforpreferentialbinding.SemiquantitativeWesternblotanalysisindicatesthatthesummationofc‐Jun,JunB,andc‐FoslevelsindifferentiatingmyeloidcellsissimilartoorexceedstheentiretyofC/EBPαandC/EBPβ,indicatingthefeasibilityofheterodimerformation.InductionofAP‐1proteinsduringmonocyticdifferentiationfavoredformationofC/EBP:AP‐1heterodimers,withC/EBPαhomodimersmoreevidentduringgranulopoiesis.Approximately350humanand300murinegenescontaintheTGACGCAAmotifbetween–2kband+1kboftheirtranscriptionstartsites.WefocusedonthemurineFosbpromoter,whichcontainsaC/EBP:AP‐1ciselementat–56and–253,withthehFOSBgenecontaininganidenticalsiteat–253anda1‐bpmismatchat–56.C/EBPα:AP‐1heterodimersboundeithersitepreferentiallyinagel‐shiftassay,C/EBPα:c‐FosERfusionproteinsinducedendogenousFosbmRNAbutnotinthepresenceofCHX,C/EBPandAP‐1proteinsboundtheendogenousFosbpromoter,mutationofthe–56ciselementreducedreporteractivityfivefold,andendogenousFosBproteinwasexpressedpreferentiallyduringmonopoiesisversusgranulopoiesis.IncreasedexpressionofJun/FosproteinselevatesC/EBP:AP‐1heterodimerformationtopotentiallyactivatenovelsetsofgenesduringmonopoiesisandpotentiallyduringotherbiologicprocesses...

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