title: Interaction of AP-1 with a cluster of NF-kappa B binding elements in the human TNF promoter region.
abstract: Transcriptional activation of the human TNF gene involves multiple regulatory elements whose functional properties vary between stimuli and cell types. Here we have used a COS-7 expression system to dissect the transactivating potential of NF-kappa B binding sites in the human TNF promoter region from other regulatory influences. In this model, NF-kappa B acts largely through a dense cluster of three binding sites located 600 nt upstream of the transcription start site. We show that the transcriptional activity of this complex is highly sensitive to the p65:p50 ratio that is expressed. We demonstrate that the AP-1 complex c-Jun/Fra2 is capable of binding to this region and that this inhibits the transactivating effects of NF-kappa B. These results are suggestive of a complex regulatory element that mediates fine control rather than acting as a simple on-off switch for TNF gene expression.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, United Kingdom. iudalova@molbiol.ox.ac.uk
authors.forename: I A
authors.initials: IA
authors.lastname: Udalova
authors.forename: D
authors.initials: D
authors.lastname: Kwiatkowski
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism; D051921:Fos-Related Antigen-2; D006801:Humans; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011401:Promoter Regions, Genetic; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017384:Sequence Deletion; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha