title: Virus Infection Induces NF-kappaB-dependent interchromosomal associations mediating monoallelic IFN-beta gene expression.
abstract: 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.
authors.affiliation: Institute of Molecular Biology, Genetics and Biotechnology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.
authors.forename: Effie
authors.initials: E
authors.lastname: Apostolou
authors.forename: Dimitris
authors.initials: D
authors.lastname: Thanos
mesh_terms: D002460:Cell Line; D002875:Chromosomes / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism
chemical_list: D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D016899:Interferon-beta