Transcriptional Profiling of Interferon Regulatory Factor 3 Target Genes: Direct Involvement in the Regulation of Interferon-Stimulated Genes

Author:

Grandvaux Nathalie12,Servant Marc J.12,tenOever Benjamin12,Sen Ganes C.3,Balachandran Siddarth4,Barber Glen N.4,Lin Rongtuan12,Hiscott John152

Affiliation:

1. Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research

2. Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada

3. Department of Molecular Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195

4. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33136

5. Departments of Microbiology and Immunology

Abstract

ABSTRACT Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly activated after virus infection and functions as a key activator of the immediate-early alpha/beta interferon (IFN) genes, as well as the RANTES chemokine gene. In the present study, a tetracycline-inducible expression system expressing a constitutively active form of IRF-3 (IRF-3 5D) was combined with DNA microarray analysis to identify target genes regulated by IRF-3. Changes in mRNA expression profiles of 8,556 genes were monitored after Tet-inducible expression of IRF-3 5D. Among the genes upregulated by IRF-3 were transcripts for several known IFN-stimulated genes (ISGs). Subsequent analysis revealed that IRF-3 directly induced the expression of ISG56 in an IFN-independent manner through the IFN-stimulated responsive elements (ISREs) of the ISG56 promoter. These results demonstrate that, in addition to its role in the formation of a functional immediate-early IFN-β enhanceosome, IRF-3 is able to discriminate among ISRE-containing genes involved in the establishment of the antiviral state as a direct response to virus infection.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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