Virus Infection Induces NF-kappaB-dependent interchromosomal associations mediating monoallelic IFN-beta gene expression

Cell. 2008 Jul 11;134(1):85-96. doi: 10.1016/j.cell.2008.05.052.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chromosomes / metabolism*
  • Enhancer Elements, Genetic*
  • Gene Expression*
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factors / metabolism
  • Interferon-beta / genetics*
  • NF-kappa B / metabolism*
  • Transcription, Genetic
  • Transfection
  • Virus Diseases / immunology*
  • Virus Diseases / metabolism


  • Interferon Regulatory Factors
  • NF-kappa B
  • Interferon-beta