Hepatocyte nuclear factor 1 binds to and transactivates the human but not the rat CYP7A1 promoter
Hepatocyte nuclear factor 1 binds to and transactivates the human but not the rat CYP7A1 promoter
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DOI：
10.1006/bbrc.1999.0980
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发表时间：
1999-07-14
影响因子：
3.1
通讯作者：
Levy-Wilson, B
中科院分区：
文献类型：
--
作者：
Chen, J;Cooper, AD;Levy-Wilson, B
胆固醇7 α-羟化酶（CYP 7A 1）是一种肝脏特异性酶，催化胆固醇降解为胆汁酸的限速步骤，因此在胆固醇稳态中起关键作用。为了阐明控制人类CYP 7A 1基因肝脏表达的机制，我们正在研究启动子区域。最初，我们观察到HepG 2细胞中启动子的总体转录活性的高达40%与人类基因的-65至-1的DNA序列相关。在该区域内，已经鉴定了肝脏富集的转录因子HNF-1（-56至-49）的结合位点。HNF-1与该位点的结合导致人启动子的转录激活。来自大鼠CYP 7A 1基因的相应片段不结合HNF-1;相反，它被孤儿受体阿普-1（COUP-TFII）和LXR α结合，这与饮食调节有关。(C)北京：科学出版社.
Cholesterol 7 alpha-hydroxylase (CYP7A1), a liver-specific enzyme, catalyzes the rate-limiting step in the degradation pathway of cholesterol to bile acids, and thus plays a key role in cholesterol homeostasis. To elucidate the mechanisms that control hepatic expression of the human CYP7A1 gene, we are studying the promoter region. Initially, we observed that up to 40% of the overall transcriptional activity of the promoter in HepG2 cells was associated with DNA sequences from -65 to -1 of the human gene. Within this region, a binding site for the liver-enriched transcription factor HNF-1 (-56 to -49) has been identified. Binding of HNF-1 to this site leads to transcriptional activation of the human promoter. The corresponding segment from the rat CYP7A1 gene does not bind HNF-1; instead, it is bound by the orphan receptors ARP-1 (COUP-TFII) and LXR alpha, that are implicated in dietary regulation. (C) 1999 Academic Press.