Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system.
Interferon (IFN) regulatory factor 1 (IRF-1) and IRF-2 were originally identified as transcription factors involved in the regulation of the IFN system. IRF-1 functions as a transcriptional activator, while IRF-2 represses IRF-1 function. More recently, evidence has been provided that IRF-1 and IRF-2 manifest antioncogenic and oncogenic properties, respectively, and that loss of one or both of the IRF-1 alleles may be critical for the development of human hematopoietic neoplasms. Both factors show a high degree of structural similarity in their N-terminal DNA-binding domains, and previous studies suggested that IRF-1 and IRF-2 bind to similar or identical cis elements within type I IFN (IFN-alpha and -beta) and IFN-inducible genes. However, the exact recognition sequences of these two factors have not yet been determined; hence, the spectrum of the IRF-responsive genes remains unclear. In this study, we determined the DNA sequences recognized by IRF-1 and IRF-2, using a polymerase chain reaction-assisted DNA-binding site selection method. We report that sequences selected by this method and the affinities for each sequence were virtually indistinguishable between IRF-1 and IRF-2. We confirm the presence of two contiguous IRF recognition sequences within the promoter region of the IFN-beta gene and of at least one such sequence in all of the IFN-inducible genes examined. Furthermore, we report the presence of potential IRF sequences in the upstream region of several genes involved in cell growth control.
Tanaka
N
N
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kawakami
T
T
Taniguchi
T
T
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007372:Interferons / Q000502:physiology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010750:Phosphoproteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
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; D007372:Interferons