...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at the transcriptional level in culture and in transgenic mice.
【24h】

Cholesterol and bile acids regulate cholesterol 7 alpha-hydroxylase expression at the transcriptional level in culture and in transgenic mice.

机译：胆固醇和胆汁酸在培养和转基因小鼠的转录水平上调节胆固醇7α-羟化酶的表达。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is the rate-limiting enzyme in bile acid biosynthesis. It is subject to a feedback control, whereby high levels of bile acids suppress its activity, and cholesterol exerts a positive control. It has been suggested that posttranscriptional control plays a major part in that regulation. We have studied the mechanisms by which cholesterol and bile acids regulate expression of the 7 alpha-hydroxylase gene and found it to be solely at the transcriptional level by using two different approaches. First, using a tissue culture system, we localized a liver-specific enhancer located 7 kb upstream of the transcriptional initiation site. We also showed that low-density lipoprotein mediates transcriptional activation of chimeric genes, containing either the 7 alpha-hydroxylase or the albumin enhancer in front of the 7 alpha-hydroxylase proximal promoter, to the same extent as the in vivo cholesterol-mediated regulation of 7 alpha-hydroxylase mRNA. In a second approach, using transgenic mice, we have found that expression of an albumin enhancer-7 alpha-hydroxylase-lacZ fusion gene is restricted to the liver and is regulated by cholesterol and bile acids in a manner quantitatively similar to that of the endogenous gene. We also found, that a liver-specific enhancer is necessary for expression of the rat 7 alpha-hydroxylase gene, in agreement with the tissue culture experiments. Together, these results demonstrate that cholesterol and bile acids regulate the expression of the 7 alpha-hydroxylase gene solely at the transcriptional level.
机译：胆固醇7α-羟化酶（7α-羟化酶）是胆汁酸生物合成中的限速酶。它受到反馈控制，从而高水平的胆汁酸抑制了其活性，而胆固醇发挥了积极的控制作用。已经提出转录后控制在该调节中起主要作用。我们研究了胆固醇和胆汁酸调节7α-羟化酶基因表达的机制，并通过使用两种不同的方法发现它仅在转录水平上。首先，使用组织培养系统，我们定位了位于转录起始位点上游7 kb的肝脏特异性增强子。我们还显示，低密度脂蛋白介导嵌合基因的转录激活，该嵌合基因在7α-羟化酶近端启动子之前含有7α-羟化酶或白蛋白增强子，其程度与体内胆固醇介导的调节有关。 7α-羟化酶mRNA。在第二种方法中，使用转基因小鼠，我们发现白蛋白增强子7α-羟化酶-lacZ融合基因的表达仅限于肝脏，并受胆固醇和胆汁酸的调控，其定量方式类似于内源性基因。我们还发现，与组织培养实验一致，肝特异性增强子对于大鼠7α-羟化酶基因的表达是必需的。总之，这些结果表明胆固醇和胆汁酸仅在转录水平上调节7α-羟化酶基因的表达。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号