Author(s): Tanaka N, Kawakami T, Taniguchi T
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Abstract 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.
This article was published in Mol Cell Biol
and referenced in Journal of Genetic Syndromes & Gene Therapy