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

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

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1
Institute of Molecular Biology, Genetics and Biotechnology, Biomedical Research Foundation, Academy of Athens, 4 Soranou Efesiou Street, Athens 11527, Greece.

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.

PMID:
18614013
DOI:
10.1016/j.cell.2008.05.052
[Indexed for MEDLINE]
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