Regulation of gene expression by cytokines and virus in human cells lacking the type‐I interferon locus

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Abstract
A number of genes that are induced by type‐I interferons are also activated by one or more other inducers, including double‐stranded RNA, viruses, interferon‐γ, interleukin‐1 and tumor necrosis factor. However, these inducers can also activate the expression of type‐I interferons. Thus, the activation of type‐I interferon‐inducible genes by these other inducers could be direct, or a secondary consequence of the induction of interferon. To distinguish between these possibilities, we have used cell lines lacking all type‐I interferon genes to study the direct effect of potential inducers on the expression of 14 interferon‐inducible human genes. We show that double‐stranded RNA, virus, interferon‐γ or tumor necrosis factor‐α can act directly to induce specific subsets of type‐I interferoninducible genes in the absence of any possible type‐I interferon involvement. The cis‐acting element which confers inducibility by type‐I interferon has been shown in some cases to confer inducibility by interferon‐γ, double‐stranded RNA or virus as well. However, not all promoters containing such an element respond to both interferon and other inducers. Thus, the ability of a given gene to respond to different inducers most likely depends on the exact nature and specific combination of cis‐acting elements present in its promoter.

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