Fujita T, Miyamoto M, Kimura Y, Hammer J, Taniguchi T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Nucleic Acids Res. 1989 May 11;17(9):3335-46. doi: 10.1093/nar/17.9.3335.
Interferon-beta (IFN-beta) gene is transcriptionally activated following virus infection of various cell types such as fibroblasts. In the previous studies, regulatory DNA sequences that mediate the virus-induced transcriptional activation have been identified within the 5'-flanking region (up to around -117 respect to the CAP site) of the human IFN-beta gene. The sequences contain binding sites (-100 to -61) for a transcriptional activator, IRF-1, the gene of which is also virus-inducible. In the present study, we focused on an additional cis-element, located between the IRF-1 binding sites and TATA box. Interestingly, the element coincides with the previously identified elements for the transcription factors H2TF-1 and NF kappa B. The element, when tandemly repeated, functions in activating the distal gene expression in either constitutive or virus-inducible manner depending on the cell type. The results suggest the importance of cooperation between IRF-1 and H2TF-1/NF kappa B-like factor in the maximal IFN-beta gene induction.
在病毒感染多种细胞类型(如成纤维细胞)后,β-干扰素(IFN-β)基因会被转录激活。在先前的研究中,已在人IFN-β基因的5'侧翼区域(相对于CAP位点约至-117)内鉴定出介导病毒诱导转录激活的调控DNA序列。这些序列包含转录激活因子IRF-1的结合位点(-100至-61),其基因也是病毒可诱导的。在本研究中,我们聚焦于位于IRF-1结合位点与TATA盒之间的另一个顺式元件。有趣的是,该元件与先前鉴定的转录因子H2TF-1和核因子κB的元件一致。该元件串联重复时,根据细胞类型以组成型或病毒诱导型方式激活远端基因表达。结果表明IRF-1与H2TF-1/核因子κB样因子之间的合作对于最大程度诱导IFN-β基因的重要性。