Neuronal and extraneuronal expression and regulation of the human α5 nicotinic receptor subunit gene
Neuronal and extraneuronal expression and regulation of the human α5 nicotinic receptor subunit gene
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DOI：
10.1046/j.1471-4159.2000.0750018.x
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发表时间：
2000-07-01
影响因子：
4.7
通讯作者：
Fornasari, D
中科院分区：
文献类型：
--
作者：
Flora, A;Schulz, R;Fornasari, D
在神经系统的几个结构中检测到编码人α 5烟碱亚基的mRNA，但似乎主要在小脑、丘脑和自主神经节中表达。第一次，α 5转录本也被检测到在几个非神经元组织，最大的表达被发现在整个胃肠道，胸腺和睾丸。许多其他的神经元位点表达α 5，但也有不表达的器官，如肝、脾和肾。为了理解控制神经元和非神经元细胞中α 5的这种多样化表达的转录机制，我们分离了人类基因的5 '调控区并表征了其性质。在这里，我们确定了α 5核心启动子，并证明它周围的DNA区域包含的元素（具有积极或消极的活动），在组织特异性的方式工作。特别地，在神经元细胞中指定5 '-非翻译区的片段具有增强子的大部分特性，因为它以位置和取向独立的方式激活异源启动子。因此，我们的结论是，α 5的表达依赖于一个高度复杂的启动子，使用不同的调控元件，以符合不同的功能和发育要求的各种组织和器官。
The mRNA encoding the human alpha 5 nicotinic subunit was detected in several structures of the nervous system but appeared to be mainly expressed in cerebellum, thalamus, and the autonomic ganglia. For the first time, the alpha 5 transcript was also detected in several nonneuronal tissues, with maximal expressions being found throughout the gastrointestinal tract, thymus, and testis. Many other extraneuronal sites expressed alpha 5, but there were also nonexpressing organs, such as the liver, spleen, and kidney. To understand the transcriptional mechanisms controlling such a diversified expression of alpha 5 in neuronal and nonneuronal cells, we isolated the 5'-regulatory region of the human gene and characterized its properties. Here we identify the alpha 5 core promoter and demonstrate that the DNA regions surrounding it contain elements (with positive or negative activities) that work in a tissue-specific fashion. In particular, the segment specifying the 5'-untranslated region in neuronal cells has most of the properties of an enhancer because it activates a heterologous promoter in a position- and orientation-independent fashion. We therefore conclude that the expression of alpha 5 relies on a highly complex promoter that uses distinct regulatory elements to comply with the different functional and developmental requirements of the various tissues and organs.