Siegrist C A, Durand B, Emery P, David E, Hearing P, Mach B, Reith W
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Mol Cell Biol. 1993 Oct;13(10):6375-84. doi: 10.1128/mcb.13.10.6375-6384.1993.
Hepatitis B virus gene expression is to a large extent under the control of enhancer I (EnhI). The activity of EnhI is strictly dependent on the enhancer factor C (EF-C) site, an inverted repeat that is bound by a ubiquitous nuclear protein known as EF-C. Here we report the unexpected finding that EF-C is in fact identical to RFX1, a novel transcription factor previously cloned by virtue of its affinity for the HLA class II X-box promoter element. This finding has allowed us to provide direct evidence that RFX1 (EF-C) is crucial for EnhI function in HepG2 hepatoma cells; RFX1-specific antisense oligonucleotides appear to inhibit EnhI-driven expression of the hepatitis B virus major surface antigen gene, and in transfection assays, RFX1 behaves as a potent transactivator of EnhI. Interestingly, transactivation of EnhI by RFX1 (EF-C) is not observed in cell lines that are not of liver origin, suggesting that the ubiquitous RFX1 protein cooperates with liver-specific factors.
乙型肝炎病毒基因表达在很大程度上受增强子I（EnhI）的控制。EnhI的活性严格依赖于增强子因子C（EF-C）位点，该位点是一个反向重复序列，被一种名为EF-C的普遍存在的核蛋白所结合。在此，我们报告了一个意外发现，即EF-C实际上与RFX1相同，RFX1是一种新型转录因子，此前因其对HLA II类X盒启动子元件的亲和力而被克隆。这一发现使我们能够提供直接证据，证明RFX1（EF-C）对HepG2肝癌细胞中EnhI的功能至关重要；RFX1特异性反义寡核苷酸似乎抑制了EnhI驱动的乙型肝炎病毒主要表面抗原基因的表达，并且在转染实验中，RFX1表现为EnhI的有效反式激活因子。有趣的是，在非肝脏来源的细胞系中未观察到RFX1（EF-C）对EnhI的反式激活，这表明普遍存在的RFX1蛋白与肝脏特异性因子协同作用。
