Interferon Regulatory Factor 1 Is Required for Mouse Gbp Gene Activation by Gamma Interferon
Open accessAbstract
Full-scale transcriptional activation of the mouse Gbp genes by gamma interferon (IFN-gamma) requires protein synthesis in embryonic fibroblasts. Although the Gbp-1 and Gbp-2 promoters contain binding sites for transcription factors Stat1 and IFN regulatory factor 1 (IRF-1), deletion analysis revealed that the Stat1 binding site is dispensable for IFN-gamma inducibility of Gbp promoter constructs in transfected fibroblasts. However, activation of the mouse Gbp promoter by IFN-gamma requires transcription factor IRF-1. Transient overexpression of IRF-1 cDNA in mouse fibroblasts resulted in high-level expression of Gbp promoter constructs. Unlike wild-type cells, IRF-1% embryonic stem cells lacking functional transcription factor IRF-1 contained very low levels of Gbp transcripts that were not increased in response to differentiation or treatment with IFN-gamma. Treatment of IRF-1% mice with IFN-gamma resulted in barely detectable levels of Gbp RNA in spleens, lungs, and livers, whereas such treatment induced high levels of Gbp RNA in the organs of wild-type mice. These observations suggest two alternative pathways for transcriptional induction of genes in response to IFN-gamma: immediate response that results from activation of preformed Stat1 and delayed response that results from induced de novo synthesis of transcription factor IRF-1.
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Self-citation
- Authors
- Briken, V., Ruffner, H., Schultz, U., Schwarz, A., Reis, L. F. L., Strehlow, I., Decker, T., & Staeheli, P.
- Affiliations
- University of Freiburg (DE)
- University of Zurich (CH)
- Vienna Biocenter (AT)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1995-02
- Volume
- 15
- Issue
- 2
- Pages
- 975-982
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC231988
- OpenAlex
- W2146736041
- Cited by
- 143
- References
- 56
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- IRF1, interferon-gamma, STAT1, transcriptional activation, promoter regulation, embryonic fibroblasts, embryonic stem cells
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cell Nucleus, DNA-Binding Proteins, Embryo, Mammalian, Fibroblasts, Gene Expression Regulation, Humans, Interferon-gamma, Mice, Inbred BALB C, Molecular Sequence Data, Oligodeoxyribonucleotides, Phosphoproteins, Promoter Regions, Genetic, Stem Cells, Transcription Factors, Transcription, Genetic, Restriction Mapping, Signal Transduction, Transcriptional Activation, Trans-Activators, Consensus Sequence, 3T3 Cells, GTP-Binding Proteins, GTP Phosphohydrolases, STAT1 Transcription Factor, Interferon Regulatory Factor-1, Mice, Rats
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