A Novel Interferon-Inducible Domain: Structural and Functional Analysis of the Human Interferon Regulatory Factor 1 Gene Promoter
Open accessAbstract
We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by gamma interferon (IFN-gamma) but more weakly and transiently by IFN-alpha. There are several putative kappa B motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN inducibility of the promoter was studied with 5' deletion mutants linked to a heterologous reporter gene. Gel mobility shift assays were used to show IFN-inducible factor binding to the IRF-1 promoter. These studies showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation. This inverted repeat binds a factor upon induction with IFN and can confer IFN inducibility on a heterologous promoter. Conversely, point mutations of the inverted repeat are not IFN inducible when linked to the same heterologous promoter.
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Interferon regulatory factor-1 is a likely candidate for sustaining Socs1 mRNA expression because it is induced by STAT1 and can associate with the Socs1 promoter to activate transcription of Socs1 mRNA.
“One likely candidate is interferon regulatory factor-1, because it is induced by STAT1 (32,42,43) and can associate with the Socs1 promoter to activate the transcription of Socs1 mRNA (18).”
From The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling (2006) · cites this paper as [32]
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- Authors
- Sims, S. H., Cha, Y., Romine, M. F., Gao, P. Q., Gottlieb, K., & Deisseroth, A. B.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Romine, M F
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1993-01
- Volume
- 13
- Issue
- 1
- Pages
- 690-702
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC358947
- OpenAlex
- W2136098448
- Cited by
- 262
- References
- 0
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 5 · 2012: 4
- FWCI
- 10.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sid W. Richardson Foundation
- National Cancer Institute (P01CA049639, P01 CA49639-O1A1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IRF1, inverted repeats, interferon-gamma induction, interferon-alpha induction, CpG islands, transcriptional regulation
- MeSH terms
- Base Sequence, Binding Sites, Cloning, Molecular, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Genes, Humans, Interferons, Molecular Sequence Data, Oligodeoxyribonucleotides, Phosphoproteins, Promoter Regions, Genetic, RNA, Messenger, Sequence Homology, Nucleic Acid, Transcription Factors, NF-kappa B, Interferon Regulatory Factor-1
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