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  • Title: Interaction of AP-1 with a cluster of NF-kappa B binding elements in the human TNF promoter region.
    Author: Udalova IA, Kwiatkowski D.
    Journal: Biochem Biophys Res Commun; 2001 Nov 23; 289(1):25-33. PubMed ID: 11708771.
    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.
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