Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB.

Transcriptional regulation of the interferon-beta (IFN-beta) gene is characterized by strict constitutive repression and virus-specific activation. Previous studies have shown that the IFN-beta promoter is constitutively repressed by a negative regulatory element (NRE). Isolated NRE acts as a constitutive and position-independent silencer on the NF-kappaB-binding sites. Here, we describe the ...
identification and functional characterization of the NRE-binding protein, called NRF (NF-kappaB-repressing factor), which abolishes the transcriptional activity of the bordering NF-kappaB- binding sites by a distance-independent mechanism. Deletion studies show that a minimal repression domain of NRF is sufficient to exert its inhibitory effect. In vitro, NF-kappaB proteins bind to purified NRF by a direct protein-protein interaction. We demonstrate that NRF is a ubiquitous and constitutive nuclear protein. In fibroblasts, the expression of the NRF antisense RNA releases the endogenous IFN-beta gene transcription. Our data strongly suggest that the NRF-mediated inhibition of NF-kappaB is a critical component of the IFN-beta gene silencing prior to viral infection.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Cell Line, Cell Nucleus, Cloning, Molecular, DNA-Binding Proteins, Female, Gene Expression Regulation, Hela Cells, Humans, Interferon-beta, Male, Molecular Sequence Data, NF-kappa B, Organ Specificity, Promoter Regions, Genetic, RNA, Messenger, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transfection
EMBO J.
Date: Nov. 15, 1999
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