Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system
Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system
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DOI：
10.1128/mcb.13.8.4531-4538.1993
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发表时间：
1993-08
影响因子：
5.3
通讯作者：
N. Tanaka;T. Kawakami;T. Taniguchi
中科院分区：
文献类型：
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作者：
N. Tanaka;T. Kawakami;T. Taniguchi
干扰素（IFN）调节因子1（IRF-1）和IRF-2最初被鉴定为参与IFN系统调节的转录因子。IRF-1作为转录激活因子发挥作用，而IRF-2抑制IRF-1的功能。最近，有证据表明IRF-1和IRF-2分别表现出抗癌和致癌特性，并且IRF-1等位基因中的一个或两个的缺失可能对人类造血肿瘤的发展至关重要。这两种因子在其N-末端DNA结合域中显示出高度的结构相似性，并且先前的研究表明IRF-1和IRF-2结合I型IFN（IFN-α和IFN-β）和IFN诱导基因内的相似或相同的顺式元件。然而，这两种因子的确切识别序列尚未确定，因此，IRF反应基因的谱仍不清楚。在这项研究中，我们确定的DNA序列识别的IRF-1和IRF-2，使用聚合酶链反应辅助DNA结合位点选择方法。我们报告说，通过这种方法选择的序列和每个序列的亲和力几乎是不可区分的IRF-1和IRF-2之间。我们确认存在两个连续的IRF识别序列内的IFN-β基因的启动子区域和至少一个这样的序列在所有的IFN-诱导基因检查。此外，我们报告的存在下，潜在的IRF序列在上游区域的几个基因参与细胞生长控制。
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.