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大鼠CYP2C13基因启动子的反式激活涉及肝细胞核因子-1(HNF-1)、肝细胞核因子-3(HNF-3)以及孤儿受体亚家族成员。

Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily.

作者信息

Legraverend C, Eguchi H, Ström A, Lahuna O, Mode A, Tollet P, Westin S, Gustafsson J A

机构信息

Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden.

出版信息

Biochemistry. 1994 Aug 23;33(33):9889-97. doi: 10.1021/bi00199a010.

Abstract

The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5' flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.

摘要

大鼠CYP2C13基因(2C13)编码参与类固醇代谢的细胞色素P-450组成型雄性形式之一。除了受发育调控外,2C13的表达局限于肝脏,并且在转录起始水平受到雌性生长激素(GH)分泌模式的抑制。在本研究中,我们表明,2C13 5'侧翼的117 bp至2 kb可重建肝脏特异性表达,但不能重建GH的调控。2C13启动子的反式激活需要HNF-1和HNF-3,并且受转录因子孤儿受体亚家族成员的影响。尽管HNF-4、ARP-1、EAR-2和COUP-TF在体外与2C13启动子结合,但EAR-2和COUP-TF的过表达而非HNF-4或ARP-1的过表达会导致非肝细胞中HNF-3和HNF-1支持的活性增强。

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