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.
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' 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.
Harada
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Takahashi
E
E
Itoh
S
S
Harada
K
K
Hori
T A
TA
Taniguchi
T
T
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D002895:Chromosomes, Human, Pair 5; D016384:Consensus Sequence; D004247:DNA / Q000032:analysis / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons; D015870:Gene Expression / Q000187:drug effects; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D016899:Interferon-beta / Q000494:pharmacology; D007372:Interferons / Q000378:metabolism*; D007438:Introns; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000276:immunology; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; C494229:IRF2 protein, human; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016899:Interferon-beta; D004247:DNA; D007372:Interferons