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T.G. Hofmann, M.L. Schmitz
The Promoter Context Determines Mutual Repression or Synergism between NF-?B and the Glucocorticoid Receptor
While the biochemical mechanisms mediating repression of NF?B activity by glucocorticoids (GCs) are relatively well studied, the role of promoter architecture for the effects of GCs on NF?B remains poorly characterized. Therefore we constructed a set of synthetic promoter reporter constructs containing various numbers of GCresponsive elements (GREs) in distinct distances to NF?B binding sites. TNF?induced activity of a synthetic promoter controlled by three NF?B binding sites was repressed by dexamethasone. The presence of only one GRE in the vicinity of the ?B sites abolished this repression and allowed synergistic transcriptional activation by NF?B and the glucocorticoid receptor (GR). The synergism identified here was not affected by the number of GREs, but strictly depends on the spacing between GREs and ?B sites. These experiments reveal that the functional interplay between NF?B and the GR also involves dependent on the promoter context synergistic stimulation of transcription.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 383, 12/2002
Pages: 1947 - 1951