Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter.
The human beta-interferon promoter contains at least two positive acting domains (PRD I and PRD II). PRD I has been previously shown to stimulate basal transcription and to respond to induction by double-stranded RNA (dsRNA). Here we show that PRD II functions independently as a constitutive element that also responds to induction. A cellular factor that specifically binds to PRD II has been identified, and the levels of this factor increase markedly in extracts from cells treated with dsRNA. The inducible factor has a binding specificity that is indistinguishable from the transcription factor NF-kappa B. As has been shown for NF-kappa B, the PRD II-specific factor can be activated in uninduced extracts by treatment with detergent, suggesting that the inactive state is due to association with an inhibitory factor. Induction by dsRNA therefore provides a novel means for the post-translational activation of NF-kappa B. Potential binding sites for NF-kappa B are present in the 5' flanking regions of a number of genes involved in the immune response, several of which are inducible by dsRNA. These findings demonstrate a role for NF-kappa B in the physiological activation of genes in non-lymphoid cells.
Visvanathan
K V
KV
Gene Expression Laboratory, Imperial Cancer Research Fund, London, UK.
Goodbourn
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D016328:NF-kappa B; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D014157:Transcription Factors; D003840:Deoxycholic Acid; D004247:DNA