Premium
Constitutive silencing of IFN‐β promoter is mediated by NRF (NF‐κB‐repressing factor), a nuclear inhibitor of NF‐κB
Author(s) -
Nourbakhsh Mahtab,
Hauser Hansjörg
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.22.6415
Subject(s) - biology , gene silencing , psychological repression , microbiology and biotechnology , transcription factor , regulation of gene expression , transcription (linguistics) , gene expression , repressor , rna interference , gene , rna , genetics , linguistics , philosophy
Transcriptional regulation of the interferon‐β (IFN‐β) gene is characterized by strict constitutive repression and virus‐specific activation. Previous studies have shown that the IFN‐β promoter is constitutively repressed by a negative regulatory element (NRE). Isolated NRE acts as a constitutive and position‐independent silencer on the NF‐κB‐binding sites. Here, we describe the identification and functional characterization of the NRE‐binding protein, called NRF (NF‐κB‐repressing factor), which abolishes the transcriptional activity of the bordering NF‐κB‐ 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‐κB 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‐β gene transcription. Our data strongly suggest that the NRF‐mediated inhibition of NF‐κB is a critical component of the IFN‐β gene silencing prior to viral infection.