Identification of a potential Nurr1 response element that activates the tyrosine hydroxylase gene promoter in cultured cells
Identification of a potential Nurr1 response element that activates the tyrosine hydroxylase gene promoter in cultured cells
复制标题
DOI：
10.1006/bbrc.2000.3204
复制
发表时间：
2000-08-11
影响因子：
3.1
通讯作者：
Kobayashi, K
中科院分区：
文献类型：
--
作者：
Iwawaki, T;Kohno, K;Kobayashi, K
酪氨酸羟化酶（TH）是儿茶酚胺生物合成的起始酶和限速酶，其基因表达在神经元发育过程中和对各种环境刺激的反应中受到转录水平的调控。Nur相关因子1（Nurr 1）是孤儿核受体超家族的一员，是中脑腹侧产生多巴胺的神经元发育和TH在这些神经元中表达所必需的。在本研究中，我们发现了一个直接激活的大鼠TH基因启动子的Nurr 1在培养的细胞系。这种激活似乎是依赖于多个调控元件赋予Nurr 1响应启动子。我们确定了一个Nurr 1响应元件（TH-NBRE 1）在TH启动子的近端区域介导的启动子的中度激活。TH-NBRE 1的序列与典型的NGFI-B反应元件高度同源。我们的研究结果表明，Nurr 1可能涉及TH基因表达的转录控制过程中的发展或响应改变的生理状态。(C)北京大学出版社.
Expression of the gene encoding tyrosine hydroxylase (TH), the initial and rate-limiting enzyme of catecholamine biosynthesis, is regulated at the transcriptional level during neuronal development and in response to a variety of environmental stimuli. Nur-related factor 1 (Nurr1), a member of the orphan nuclear receptor superfamily, is required for development of dopamine-producing neurons in the ventral midbrain and for expression of TH in these neurons. In the present study, we found a direct activation of the rat TH gene promoter by Nurr1 in cultured cell lines. This activation appeared to be dependent on multiple regulatory elements conferring Nurr1 responsiveness to the promoter. We identified a Nurr1 response element (TH-NBRE1) in the proximal region of the TH promoter that mediates a moderate activation of the promoter. The sequence of TH-NBRE1 was highly homologous to that of the typical NGFI-B response element. Our findings suggest that Nurr1 may be implicated in the transcriptional control of TH gene expression during development or in response to altered physiological states. (C) 2000 Academic Press.