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首页> 外文期刊>Molecular and Cellular Biology >The POU homeodomain transcription factor Oct-1 is essential for activity of the gonadotropin-releasing hormone neuron-specific enhancer.
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The POU homeodomain transcription factor Oct-1 is essential for activity of the gonadotropin-releasing hormone neuron-specific enhancer.

机译：POU同源域转录因子Oct-1对于促性腺激素释放激素神经元特异性增强子的活性至关重要。

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The mechanisms of specification of gene expression in a complex tissue such as the brain remain poorly understood. To provide a model system for the study of gene regulation in a specific subpopulation of differentiated neurons, we have derived cell lines from tumors created in transgenic mice by targeting simian virus 40 T antigen expression by using the regulatory regions of the gene for gonadotropin-releasing hormone (GnRH), a decapeptide released from specialized neurons in the hypothalamus. Transfections into the cultured GnRH-secreting hypothalamic neuronal cell line GT1 have identified a neuron-specific enhancer, 1.5 kb upstream of the GnRH gene, which binds multiple GT1 nuclear proteins. In particular, one AT-rich protein-binding region, AT-a, is critical for enhancer activity. In this study, we used electrophoretic mobility shift assays to detect a GT1 nuclear protein complex that binds the AT-a region. Close inspection of the AT-a bottom-strand sequence revealed homology to the octamer motif, a sequence known to bind members of the POU homeodomain transcription factor family. Although we demonstrate expression of a number of POU homeodomain genes in GT1 cells, a supershift assay with Oct-1 antibody demonstrates that Oct-1 is the protein binding the enhancer. Finally, specific mutations in the AT-a region that affected Oct-1 binding were correlated with decreased transcription. Thus, Oct-1 binds to the GnRH enhancer in vitro, and this binding is critical to the transcriptional activity of this neuron-specific enhancer in GT1 cells.
机译：在诸如大脑的复杂组织中，基因表达规范的机制仍然知之甚少。为了提供用于研究分化的神经元的特定亚群中的基因调控的模型系统，我们已经通过使用促性腺激素释放基因的调控区域靶向猿猴病毒40 T抗原表达而从转基因小鼠中创建的肿瘤中衍生了细胞系激素（GnRH），一种从下丘脑的特定神经元释放的十肽。转染到培养的分泌GnRH的下丘脑神经元细胞系GT1中，已鉴定出一种神经元特异性增强子，位于GnRH基因上游1.5 kb，与多个GT1核蛋白结合。特别地，一个富含AT的蛋白质结合区域AT-a对于增强子活性至关重要。在这项研究中，我们使用电泳迁移率变动分析法检测结合AT-a区域的GT1核蛋白复合物。对AT-a底链序列的仔细检查显示与八聚体基序同源，该序列已知与POU同源域转录因子家族成员结合。尽管我们证明了GT1细胞中许多POU同源结构域基因的表达，但是用Oct-1抗体进行的超位移分析表明Oct-1是结合增强子的蛋白质。最后，影响Oct-1结合的AT-a区域中的特定突变与转录降低相关。因此，Oct-1在体外与GnRH增强子结合，这种结合对于该神经元特异性增强子在GT1细胞中的转录活性至关重要。

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