PMID- 10562553 OWN - NLM STAT- MEDLINE DCOM- 20000120 LR - 20081121 IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 18 IP - 22 DP - 1999 Nov 15 TI - Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB. PG - 6415-25 AB - 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. FAU - Nourbakhsh, M AU - Nourbakhsh M AD - Department of Gene Regulation and Differentiation, GBF-National Research Institute for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. FAU - Hauser, H AU - Hauser H LA - eng SI - GENBANK/AJ011812 PT - Journal Article PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (DNA-Binding Proteins) RN - 0 (NF-kappa B) RN - 0 (NKRF protein, human) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) RN - 77238-31-4 (Interferon-beta) SB - IM MH - Amino Acid Sequence MH - Base Sequence MH - Cell Line MH - Cell Nucleus/*metabolism MH - Cloning, Molecular MH - DNA-Binding Proteins/metabolism MH - Female MH - *Gene Expression Regulation MH - HeLa Cells MH - Humans MH - Interferon-beta/biosynthesis/*genetics MH - Male MH - Molecular Sequence Data MH - NF-kappa B/*antagonists & inhibitors MH - Organ Specificity MH - *Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Recombinant Proteins/biosynthesis MH - Repressor Proteins/*metabolism MH - Transcription Factors/*metabolism MH - Transfection PMC - PMC1171704 EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] AID - 10.1093/emboj/18.22.6415 [doi] PST - ppublish SO - EMBO J. 1999 Nov 15;18(22):6415-25. doi: 10.1093/emboj/18.22.6415.