RETINOID-X RECEPTOR RXR-ALPHA BINDS TO AND TRANSACTIVATES THE HEPATITIS-B VIRUS ENHANCER
RETINOID-X RECEPTOR RXR-ALPHA BINDS TO AND TRANSACTIVATES THE HEPATITIS-B VIRUS ENHANCER
复制标题
DOI：
10.1073/pnas.89.19.9059
复制
发表时间：
1992-10-01
影响因子：
11.1
通讯作者：
SIDDIQUI, A
中科院分区：
文献类型：
--
作者：
HUAN, BF;SIDDIQUI, A
在功能上定义的B型肝炎病毒（HBV）增强子元件内，存在一个类维生素A X受体（RXR）反应元件。基因分析显示，含有该区域的增强子的一个短片段在增强子功能的调节中发挥关键作用，并代表肝脏特异性活性的主要决定因素。肝脏特异性受体RXR α的全长蛋白质和DNA结合域都与HBV增强子中假定的视黄酸反应元件结合。在体内，当与RXR α表达载体共转染时，HBV增强子-报告基因构建体对维甲酸的诱导有应答。HBV视黄酸反应元件中的单碱基转换（G -> A）导致RXR α的体外结合活性和HBV增强子的体内活性均显著降低。因此，视黄酸和RXR α被认为是HBV基因表达的肝脏特异性调节和由此产生的疾病发病机制中的重要决定因素。
A retinoid X receptor (RXR) response element was located within the functionally defined hepatitis B virus (HBV) enhancer element. A short segment of the enhancer that contains this region has been shown with genetic analysis to play a key role in the regulation of enhancer function and to represent a major determinant of liver-specific activity. Both the full-length protein and the DNA-binding domain of the liver-specific receptor RXRalpha bound to the putative retinoic acid response element in the HBV enhancer. In vivo, an HBV enhancer-reporter gene construct responds to induction with retinoic acid when cotransfected with an RXRalpha expression vector. A single-base transition (G --> A) in the HBV retinoic acid response element leads to a dramatic reduction both in the in vitro binding activity of RXRalpha and the in vivo activity of the HBV enhancer. Thus, retinoic acid and the RXRalpha are implicated as being significant determinants in the liver-specific regulation of HBV gene expression and the resultant disease pathogenesis.