An evolutionary conserved COUP-TF binding element in a neural-specific gene and COUP-TF expression patterns support a major role for COUP-TF in neural development.
An evolutionary conserved COUP-TF binding element in a neural-specific gene and COUP-TF expression patterns support a major role for COUP-TF in neural development.
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DOI：
10.1210/mend.8.12.7708064
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发表时间：
1994-12
影响因子：
--
通讯作者：
X. Lu;G. Salbert;M. Pfahl
中科院分区：
文献类型：
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作者：
X. Lu;G. Salbert;M. Pfahl
COUP 转录因子（COUP-TF 和 ARP-1）是整个进化过程中核受体超家族中最高度保守的成员。先前的研究表明COUP孤儿受体可能参与果蝇和斑马鱼的早期神经发生。在这里，我们鉴定了一个神经特异性基因，视紫红质抑制蛋白，其转录可以通过位于转录起始位点上游的 DR-7 元件（具有 7 个碱基对间隔区的直接重复）受到内源性 COUP 的调节。重要的是，抑制蛋白基因启动子的 COUP 结合位点在小鼠、牛和人类中是保守的。然而，小鼠元件也能够对视黄酸做出反应，而人类基因中的元件则不能。 COUP-TF 的表达与体内已知的抑制蛋白基因表达位点相关，特别是在视网膜分化期间。我们还表明，COUP-TF 在胚胎发生过程中在小鼠中枢神经系统中以时空定义的模式表达。看来，COUP-TF 的表达模式在发育中大脑的某些区域是独特的，这表明 COUP-TF 和/或 ARP-1 具有新的作用，不同于它们在限制其他激素信号传导途径中的作用。我们的数据表明，COUP 在控制发育过程中神经特异性程序子集方面发挥着至关重要的作用。
The COUP transcription factors (COUP-TF and ARP-1) are the most highly conserved members of the nuclear receptor superfamily throughout evolution. Previous studies indicated that COUP orphan receptors may be involved in early neurogenesis in Drosophila and zebrafish. Here we identified a neural-specific gene, arrestin, whose transcription can be regulated by endogenous COUPs through a DR-7 element (direct repeat with a 7-base pair spacer) located upstream of the transcription start site. Importantly, the COUP binding site of the arrestin gene promoter is conserved among mouse, bovine, and human. However, the mouse element is also capable of responding to retinoic acid while the element in the human gene does not. Expression of COUP-TF correlates with the known expression sites of the arrestin gene in vivo, notably during the differentiation of the retina. We also show that COUP-TF is expressed in a spatio-temporally defined pattern in the murine central nervous system during embryogenesis. It appears that the expression pattern of COUP-TF is unique in certain regions of the developing brain, which would indicate a novel role for COUP-TF and/or ARP-1, distinct from their role in restricting other hormonal signaling pathways. Together our data suggest that COUPs play a crucial role in controlling a subset of neural-specific programs during development.