A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains.
A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains.
复制标题
大鼠催产素启动子中的负视黄酸反应元件限制异源反式激活结构域的转录刺激。
DOI：
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发表时间：
1992
影响因子：
11.1
通讯作者：
M. Rosenfeld
中科院分区：
文献类型：
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作者：
S. Lipkin;C. Nelson;C. Glass;M. Rosenfeld
视黄酸受体是配体依赖性转录因子，其刺激来自含有视黄酸或甲状腺激素应答元件的启动子的基因转录。我们描述了一个高亲和力的结合位点，从大鼠催产素启动子介导的负转录调控的视黄酸受体。为了检查是否强大的，组成性的反式激活结构域将能够刺激基因转录时，结合到这个DNA结合位点，通常介导转录抑制，我们融合的反式激活结构域的单纯疱疹病毒蛋白VP 16的氨基端的视黄酸受体和测试的活性的嵌合蛋白的负视黄酸反应元件。这种嵌合的视黄酸受体作为一个强大的，组成型反式激活因子结合到启动子含有回文甲状腺激素/视黄酸反应元件，但令人惊讶的是，它仍然抑制基因转录结合到启动子含有催产素阴性视黄酸反应元件。这些结果表明，一个负的DNA结合位点本身可以抑制甚至有效的组成型反式激活结构域的功能，并提供证据表明，一个组成型反式激活结构域的拴系到DNA是不足以激活基因转录。
Retinoic acid receptors are ligand-dependent transcription factors that stimulate gene transcription from promoters containing retinoic acid or thyroid hormone response elements. We describe a high-affinity binding site from the rat oxytocin promoter that mediates negative transcriptional regulation by the retinoic acid receptor. To examine whether strong, constitutive transactivation domains would be capable of stimulating gene transcription when bound to this DNA binding site that normally mediates transcriptional repression, we fused the transactivation domain of the herpes simplex viral protein VP16 to the amino terminus of the retinoic acid receptor and tested the activity of the chimeric protein on the negative retinoic acid response element. This chimeric retinoic acid receptor acted as a strong, constitutive transactivator when bound to promoters containing palindromic thyroid hormone/retinoic acid response elements but surprisingly it still repressed gene transcription when bound to promoters containing the oxytocin-negative retinoic acid response element. These results suggest that a negative DNA binding site itself can inhibit the function of even potent constitutive transactivation domains, and provide evidence that tethering of a constitutive transactivation domain to DNA is insufficient to activate gene transcription.