Differential configurations involving binding of USF transcription factors and Twist1 regulate Alx3 promoter activity in mesenchymal and pancreatic cells
Differential configurations involving binding of USF transcription factors and Twist1 regulate Alx3 promoter activity in mesenchymal and pancreatic cells
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DOI：
10.1042/bj20120962
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发表时间：
2013-02-15
影响因子：
4.1
通讯作者：
Vallejo, Mario
中科院分区：
文献类型：
--
作者：
Garcia-Sanz, Patricia;Fernandez-Perez, Antonio;Vallejo, Mario
在胚胎发育过程中，无芒型同源结构域蛋白Alx 3在前额间充质中表达，并有助于调节颅面发育。在成人中，Alx 3在胰岛中表达，在胰岛中它参与葡萄糖稳态的控制。在本研究中，我们研究了这两种细胞类型中Alx 3基因表达的转录调控。我们发现Alx 3启动子包含两个E-box调控元件，命名为EB 1和EB 2，它们为基本螺旋环螺旋转录因子Twist 1、E47、USF（上游刺激因子）1和USF 2提供结合位点。在从前额分离的原代小鼠胚胎间充质细胞中，EB 2与Twist 1结合，而EB 1与USF 1和USF 2结合。EB 1和EB 2的完整性是Twist 1介导的Alx 3启动子的反式激活所必需的，即使Twist 1不结合EB 1，这表明USF 1和USF 2与该元件的结合是Twist 1依赖性Alx 3启动子活性所必需的。相反，在胰岛胰岛素产生细胞中，EB 2的完整性对于近端启动子活性是不需要的。本研究的结果表明，USF 1和USF 2是重要的调节因子Alx 3基因在不同类型的细胞中的表达，而Twist 1有助于间充质细胞中的转录反式激活，而不是在胰腺细胞中。
During embryonic development, the aristaless-type homeodomain protein Alx3 is expressed in the forehead mesenchyme and contributes to the regulation of craniofacial development. In the adult, Alx3 is expressed in pancreatic islets where it participates in the control of glucose homoeostasis. In the present study, we investigated the transcriptional regulation of Alx3 gene expression in these two cell types. We found that the Alx3 promoter contains two E-box regulatory elements, named EB1 and EB2, that provide binding sites for the basic helix loop helix transcription factors Twist1, E47, USF (upstream stimulatory factor) 1 and USF2. In primary mouse embryonic mesenchymal cells isolated from the forehead, EB2 is bound by Twist1, whereas EB1 is bound by USF1 and USF2. Integrity of both EB1 and EB2 is required for Twistl-mediated transactivation of the Alx3 promoter, even though Twist1 does not bind to EB1, indicating that binding of USF1 and USF2 to this element is required for Twist1-dependent Alx3 promoter activity. In contrast, in pancreatic islet insulin-producing cells, the integrity of EB2 is not required for proximal promoter activity. The results of the present study indicate that USF1 and USF2 are important regulatory factors for Alx3 gene expression in different cell types, whereas Twist1 contributes to transcriptional transactivation in mesenchymal, but not in pancreatic, cells.