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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.

Original publication

DOI

10.1006/bbrc.2001.5929

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

23/11/2001

Volume

289

Pages

25 - 33

Keywords

Animals, Binding Sites, COS Cells, DNA-Binding Proteins, Fos-Related Antigen-2, Humans, NF-kappa B, NF-kappa B p50 Subunit, Promoter Regions, Genetic, Protein Subunits, Proto-Oncogene Proteins c-fos, Proto-Oncogene Proteins c-jun, Sequence Deletion, Transcription Factor AP-1, Transcription Factor RelA, Transcription Factors, Transcriptional Activation, Tumor Necrosis Factor-alpha