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首页> 外文期刊>Cellular Physiology and Biochemistry >The Human Pendrin Promoter Contains two N4 GAS Motifs with Different Functional Relevance
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The Human Pendrin Promoter Contains two N4 GAS Motifs with Different Functional Relevance

机译：人类Pendrin启动子包含两个具有不同功能相关性的N4 GAS母题

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Background: Pendrin, an anion exchanger associated with the inner ear, thyroid and kidney, plays a significant role in respiratory tissues and diseases, where its expression is increased following IL-4 and IL-13 exposure. The mechanism leading to increased pendrin expression is in part due to binding of STAT6 to a consensus sequence (N4 GAS motif) located in the pendrin promoter. As retrospective analyses of the 5' upstream sequence of the human pendrin promoter revealed an additional N4 GAS motif (1660 base pairs upstream of the one previously identified), we set out to define its contribution to IL-4 stimulated changes in pendrin promoter activity. Methods and Results: Electrophoretic mobility shift assays showed that STAT6 bound to oligonucleotides corresponding to both N4 GAS motifs in vitro, while dual luciferase promoter assays revealed that only one of the N4 GAS motifs was necessary for IL-4 -stimulated increases in pendrin promoter activity in living cells. We then examined the ability of STAT6 to bind each of the N4 GAS motifs in vivo with a site-specific ChIP assay, the results of which showed that STAT6 interacted with only the N4 GAS motif that was functionally implicated in increasing the activity of the pendrin promoter following IL-4 treatment. Conclusions: Of the two N4 GAS motifs located in the human pendrin promoter region analyzed in this study (nucleotides -3906 to +7), only the one located nearest to the first coding ATG participates in IL-4 stimulated increases in promoter activity.
机译：背景：Pendrin是与内耳，甲状腺和肾脏相关的阴离子交换剂，在呼吸组织和疾病中起着重要作用，在IL-4和IL-13暴露后其表达增加。导致Pendrin表达增加的机制部分是由于STAT6与Pendrin启动子中的共有序列（N 4 GAS基序）结合所致。由于对人pendrin启动子5'上游序列的回顾性分析揭示了另外的N 4 GAS基序（先前鉴定到的一个1660个碱基对），我们着手确定其对IL-的贡献4刺激了pendrin启动子活性的改变。方法和结果：电泳迁移率迁移分析表明，STAT6在体外与对应于两个N 4 GAS基序的寡核苷酸结合，而双荧光素酶启动子分析表明，只有N 4 之一> GAS图案对于IL-4刺激活细胞中pendrin启动子活性的增加是必需的。然后，我们通过位点特异性ChIP分析检测了STAT6体内结合N 4 个GAS模体的能力，结果表明STAT6仅与N 4 <在功能上与IL-4处理后的pendrin启动子的活性有关的GAS基序。结论：在这项研究中分析的位于人Pendrin启动子区域的两个N 4 GAS基序（核苷酸-3906至+7）中，只有最靠近第一个编码ATG的一个参与了IL- 4刺激启动子活性增加。

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