Glucocorticoid receptor mediated repression of human insulin gene expression is regulated by PGC-1α
Glucocorticoid receptor mediated repression of human insulin gene expression is regulated by PGC-1α
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DOI：
10.1016/j.bbrc.2006.11.074
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发表时间：
2007-01-19
影响因子：
3.1
通讯作者：
Lee, In-Kyu
中科院分区：
文献类型：
--
作者：
Jang, Won Gu;Kim, Eun Jung;Lee, In-Kyu
胰岛素基因的转录调控在维持胰腺β细胞响应各种刺激的功能中起关键作用。在这里，我们使用INS-1细胞来测试PGC-1 α通过调节糖皮质激素（GR）与胰岛素基因启动子的结合来调节人胰岛素基因转录的假设。对人胰岛素启动子区的分析显示，由GR和PGC-1 α调节的抑制区位于-362至-257 bp。为了定位GR结合位点在人胰岛素启动子区，用候选GR结合序列进行EMSA，并证实回文区（Palin，-284至-274 bp）与GR特异性相互作用。我们还发现GR的Palin结合活性在PGC-1 α存在下增加。这些发现表明，PGC-1 α提高了GR与Palin的结合，从而增强了GR介导的对人胰岛素转录的抑制。(c)2006 Elsevier Inc保留所有权利。
Transcriptional regulation of the insulin gene plays a critical role in maintenance of pancreatic beta cell function in response to various stimuli. Here, we used INS-1 cells to test the hypothesis that PGC-1 alpha regulates human insulin gene transcription by modulating glucocorticoid (GR) binding to the insulin gene promoter. Analysis of the human insulin promoter region revealed that the suppressive region regulated by GR and PGC-1 alpha is localized from -362 to -257 bp. To locate the GR binding site in the human insulin promoter region, EMSAs were performed with candidate GR binding sequences and confirmed that a palindromic region (Palin, -284 to -274 bp) ;specifically interacts with GR. We also found that the Palin-binding activity of GR is increased in the presence of PGC-1 alpha. These findings suggest that PGC-1 alpha elevates the binding of GR to Palin and thereby enhances the GR-mediated inhibition of human insulin transcription. (c) 2006 Elsevier Inc All rights reserved.