The repressive function of AP2 transcription factor on the hepatocyte growth factor gene promoter
The repressive function of AP2 transcription factor on the hepatocyte growth factor gene promoter
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DOI：
10.1006/bbrc.2000.2848
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发表时间：
2000-06-16
影响因子：
3.1
通讯作者：
Zarnegar, R
中科院分区：
文献类型：
--
作者：
Jiang, JG;DeFrances, MC;Zarnegar, R
肝细胞生长因子是一种重要的多功能生长因子，其基因表达在转录水平上受到严格调控。我们实验室之前的研究表明，HGF 基因的启动子和近端启动子区域存在多个顺式作用元件。在这项研究中，我们发现AP2转录因子特异性结合位于HGF基因启动子上游区域-230至-260的调控位点。凝胶迁移和超级迁移测定证实 AP2 与该区域具有高结合亲和力。在 AP2 核心结合区引入突变的功能研究以及使用 AP2 表达载体的共转染实验表明，AP2 对 HGF 基因启动子活性发挥抑制作用。 AP2 结合位点与 NF1 和 USF/E-box 结合位点重叠，我们最近证明它们构成了 NF1 和 USF 转录因子家族成员的复合多功能对接位点。不同细胞系中 AP2 与该复合位点的结合活性与 HGF 基因表达之间存在负相关。因此，APS介导的HGF基因启动子抑制可能是负责调节HGF表达的分子机制的一部分。 (C) 2000 年学术出版社。
Hepatocyte growth factor is an important multifunctional growth factor whose gene expression is tightly regulated at the transcriptional level. Previous studies from our laboratory have shown that several cis-acting elements are present in the promoter and proximal promoter region of the HGF gene. In this study, we have uncovered that AP2 transcription factor specifically binds to a regulatory site located at -230 to -260 in the upstream region of the HGF gene promoter. Gelshift and supershift assays confirmed that AP2 has high binding affinity to this region. Functional studies which introduced a mutation in the AP2 core binding region as well as cotransfection experiments using an AP2 expression vector revealed that AP2 exerts a repressive role on the HGF gene promoter activity. The AP2 binding site overlaps with those of NF1 and USF/E-box binding sites which we have recently shown to constitute a composite multifunctional docking site for the members of the NF1 and USF transcription factor families. An inverse correlation was noted between AP2 binding activity to this composite site and HGF gene expression in different cell lines. Therefore, APS-mediated repression of the HGF gene promoter may be part of the molecular mechanism responsible for regulating HGF expression. (C) 2000 Academic Press.