An enhancer element 6 kb upstream of the mouse HNF4α1 promoter is activated by glucocorticoids and liver-enriched transcription factors
An enhancer element 6 kb upstream of the mouse HNF4α1 promoter is activated by glucocorticoids and liver-enriched transcription factors
复制标题
DOI：
10.1093/nar/29.17.3495
复制
发表时间：
2001-09-01
影响因子：
14.9
通讯作者：
Weiss, MC
中科院分区：
文献类型：
--
作者：
Bailly, A;Torres-Padilla, ME;Weiss, MC
我们已经表征了相对于HNF 4 α 1转录起始约6 kb的700 bp增强子元件。该元件在分化的肝癌细胞中增加活性并赋予异源以及同源启动子糖皮质激素诱导，并且在去分化的肝癌细胞中被HNF 4 α 1、HNF 4 α 7、HNF 1 α和HNF 1 β反式激活。一个240 bp的亚区保留了基础和增强子诱导的活性。其含有HNF 1、HNF 4、HNF 3和C/EBP结合位点，如DNA酶I足迹法和使用核提取物和/或重组HNF 1 α和HNF 4 α 1的电泳迁移率变动试验所示。突变分析表明，HNF 1位点是HNF 1 α反式激活所必需的，并且是完全基础增强子活性所必需的，C/EBP位点也是如此。与C/EBP、HNF 4和HNF 3位点重叠的糖皮质激素反应元件共有位点对于最佳激素诱导至关重要。我们提出了一个模型，占弱表达HNF 4 α 1在胚胎肝脏和强表达在新生儿/成人肝脏通过增强子中确定的结合位点。
We have characterized a 700 bp enhancer element around -6 kb relative to the HNF4 alpha1 transcription start. This element increases activity and confers glucocorticoid induction to a heterologous as well as the homologous promoters in differentiated hepatoma cells and is transactivated by HNF4 alpha1, HNF4 alpha7, HNF1 alpha and HNF1 beta in dedifferentiated hepatoma cells. A 240 bp sub-region conserves basal and hormone-induced enhancer activity. It contains HNF1, HNF4, HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic mobility shift assays using nuclear extracts and/or recombinant HNF1 alpha and HNF4 alpha1. Mutation analyses showed that the HNF1 site is essential for HNF1 alpha transactivation and is required for full basal enhancer activity, as is the C/EBP site. Glucocorticoid response element consensus sites which overlap the C/EBP, HNF4 and HNF3 sites are crucial for optimal hormonal induction. We present a model that accounts for weak expression of HNF4 alpha1 in the embryonic liver and strong expression in the newborn/adult liver via the binding sites identified in the enhancer.