Iwawaki T, Kohno K, Kobayashi K
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0101, Japan.
Biochem Biophys Res Commun. 2000 Aug 11;274(3):590-5. doi: 10.1006/bbrc.2000.3204.
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.
酪氨酸羟化酶（TH）是儿茶酚胺生物合成的起始和限速酶，其编码基因的表达在神经元发育过程中以及对多种环境刺激的反应中受到转录水平的调控。孤儿核受体超家族成员Nur相关因子1（Nurr1）是腹侧中脑多巴胺能神经元发育以及这些神经元中TH表达所必需的。在本研究中，我们发现在培养的细胞系中Nurr1可直接激活大鼠TH基因启动子。这种激活似乎依赖于赋予启动子对Nurr1反应性的多个调控元件。我们在TH启动子近端区域鉴定出一个Nurr1反应元件（TH-NBRE1），它介导启动子的适度激活。TH-NBRE1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，Nurr1可能参与发育过程中或对生理状态改变的反应中TH基因表达的转录调控。
