Constitutive silencing of IFN-β promoter is mediated by NRF (NF-κB-repressing factor), a nuclear inhibitor of NF-κB

Open Access
Publisher Website
Google Scholar
Abstract
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.