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Regulation of type I interferon gene expression by interferon regulatory factor-3
S L Schafer1, R Lin, P A Moore
1Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21231, USA.
The Journal of Biological Chemistry
|February 28, 1998
Summary
Interferon regulatory factor 3 (IRF-3) binds to IFN gene promoters but does not activate them alone. IRF-3 cooperates with RelA(p65) to stimulate the IFNB promoter, but inhibits IFNA4 promoter activity.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Interferon (IFN) regulatory factors (IRFs) are transcription factors crucial for IFN and interferon-stimulated gene (ISG) expression.
- IRF binding sites in IFNA and IFNB promoters suggest their role in virus-mediated gene induction.
- A novel human IRF, IRF-3, binds to the ISG15 promoter and activates transcription.
Purpose of the Study:
- To investigate the role of IRF-3 in modulating IFNA and IFNB promoter activity.
- To determine if IRF-3 can activate IFNA and IFNB gene transcription.
Main Methods:
- IRF-3 binding to IFNA4 and IFNB promoter regions was assessed.
- Transcriptional activity of IFNA4 and IFNB promoters was measured using IRF-3 and fusion proteins.
- Cotransfection experiments with IRF-3, RelA(p65), and IRF-1 were performed.
Main Results:
- IRF-3 binds to IFNA4 and IFNB promoter regions but does not stimulate their activity alone in 293 cells.
- A fusion protein of IRF-3 and RelA(p65) activated both IFNA4 and IFNB promoters.
- IRF-3 and RelA(p65) cotransfection activated the IFNB promoter but not IFNA4.
- IRF-3 inhibited virus- and IRF-1-mediated IFNA4 promoter activation.
Conclusions:
- IRF-3 does not directly stimulate IFN gene expression in 293 cells.
- IRF-3 can cooperate with RelA(p65) to activate the IFNB promoter.
- IRF-3 exhibits inhibitory effects on IFNA4 promoter activation under certain conditions.