Interferon regulatory factor 1 induces the expression of the interferon‐stimulated genes

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Abstract
The interferon regulatory factor 1 (IRF‐1) is a positive transcriptional regulatory protein which acts in the interferon signal transduction pathway to activate the transcription of the type I interferon genes by binding to the PRDI response element. The aim of this study was to explore the role of IRF‐1 in regulating the expression of other interferon‐stimulated genes in the interferon signal transduction pathway. A transient transfection assay was used to show that IRF‐1 induced the expression of interferon‐stimulated genes. The induction was a direct result of IRF‐1 binding to the promoters of the interferon‐stimulated response element (ISRE). The levels of endogenous mRNA of two interferon‐stimulated genes, 6‐16 and 9‐27, were increased in cells containing increased levels of IRF‐1. In addition, IRF‐1 activates the expression of IRF‐2, a negative regulator of the type I interferon genes themselves. Two sequences were found in the IRF‐2 promoter which were the binding sites for IRF‐1. Mutations in the oligonucleotide sequences of these sites could abolish the binding of the IRF‐1. These data suggested that IRF‐1 not only plays an important role in the induction of type I interferon genes, but also in the activation of interferon‐stimulated genes.

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