Structure and regulation of the human interferon regulatory factor 1 (IRF-1) and IRF-2 genes: Implications for a gene network in the interferon system
- Osaka Univ., Suita-shi (Japan); and others
Interferon regulatory factor 1 (IRF-1) and IRF-2 are structurally similar DNA-binding factors which were originally identified as regulators of the type I interferon (IFN) system; the former functions as a transcriptional activator, and the latter represses IRF-1 function by competing for the same cis elements. More recent studies have revealed new roles of the two factors in the regulation of cell growth; IRF-1 and IRF-2 manifest antioncogenic and oncogenic activities, respectively. In this study, we determined the structures and chromosomal locations of the human IRF-1 and IRF-2 genes and further characterized the promoters of the respective genes. Comparison of exon-intron organization of the two genes revealed a common evolutionary structure, notably within the exons encoding the N-terminal portions of the two factors. We confirmed the chromosomal mapping of the human IRF-1 gene to 5q31.1 and newly assigned the IRF-2 gene to 4q35.1, using fluorescence in situ hybridization. The 5{prime} regulatory regions of both genes contain highly GC-rich sequences and consensus binding sequences for several known transcription factors, including NF-{kappa}B. Interestingly, one IRF binding site was found within the IRF-2 promoter, and expression of the IRF-2 gene was affected by both transient and stable IRF-1 expression. In addition, one potential IFN-{gamma}-activated sequence was found within the IRF-1 promoter. Thus, these results may shed light on the complex gene network involved in regulation of the IFN system. 61 refs., 7 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 577154
- Journal Information:
- Molecular and Cellular Biology, Journal Name: Molecular and Cellular Biology Journal Issue: 2 Vol. 14; ISSN 0270-7306; ISSN MCEBD4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
ANIMAL CELLS
BIOLOGICAL EVOLUTION
CELL DIFFERENTIATION
DNA SEQUENCING
DNA-CLONING
EXONS
FLUORESCENCE
GENE REGULATION
GENE REPRESSORS
GENES
GENETIC MAPPING
GROWTH
HUMAN CHROMOSOME 5
HUMAN CHROMOSOMES
IN-SITU HYBRIDIZATION
INTERFERON
INTRONS
NUCLEOTIDES
ONCOGENIC TRANSFORMATIONS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION FACTORS