Virus Infection Induces NF-κB-Dependent Interchromosomal Associations Mediating Monoallelic IFN-β Gene Expression

Transcriptional activation of the IFN-β gene by virus infection requires the cooperative assembly of an enhanceosome. We report that the stochastic and monoallelic expression of the IFN-β gene depends on interchromosomal associations with three identified distinct genetic loci that could mediate binding of the limiting transcription factor NF-κB to the IFN-β enhancer, thus triggering enhanceosome assembly and activation of transcription from this allele. The probability of a cell to express IFN-β is dramatically increased when the cell is transfected with any of these loci. The secreted IFN-β protein induces high-level expression of the enhanceosome factor IRF-7, which in turn promotes enhanceosome assembly and IFN-β transcription from the remaining alleles and in other initially nonexpressing cells. Thus, the IFN-β enhancer functions in a nonlinear fashion by working as a signal amplifier.