The rat arylalkylamine N-acetyltransferase E-box:: differential use in a master vs. a slave oscillator

The rat arylalkylamine N-acetyltransferase E-box:: differential use in a master vs. a slave oscillator
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DOI:
10.1016/s0169-328x(00)00160-1
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发表时间:
2000-09-30
期刊:
MOLECULAR BRAIN RESEARCH
影响因子:
--
通讯作者:
Baler, R
Baler, R
中科院分区:
其他
文献类型:
--
作者:
Chen, W;Baler, R

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大鼠芳烷基胺 N-乙酰转移酶 (AA-NAT) 基因编码关键酶,其节律性表达驱动夜间褪黑激素的产生。有趣的是,这种酶实际上只在两种系统发育相关的组织中表达:视网膜光感受器,其具有内源性时钟;以及松果体细胞,在高等脊椎动物中,其功能严格响应视交叉上核(SCN)中的主振荡器。虽然人们对大鼠松果体(从属振荡器)中的 AA-NAT 转录调控了解很多,但对通过时钟控制视网膜中 AA-NAT 基因表达的机制缺乏充分的了解。在本研究中,我们在大鼠 AA-NAT 基因的第一个内含子中鉴定了一个功能性 E 盒,它能够通过 bMAL/CLOCK 异二聚体的作用介导转录上调。这是第一份将 AA-NAT 基因描述为主振荡器中生物钟环路的可能直接转录目标的报告。 (C) 2000 Elsevier Science B.V. 保留所有权利。
The rat arylalkylamine N-acetyltransferase (AA-NAT) gene encodes the key enzyme whose rhythmic expression drives the nocturnal production of melatonin. It is of interest that this enzyme is expressed virtually exclusively in two phylogenetically related tissues: retinal photoreceptors, which harbor an endogenous clock, and pinealocytes which, in higher vertebrates, function strictly in response to the master oscillator in the suprachiasmatic nucleus (SCN). While much is known about AA-NAT transcriptional regulation in the rat pineal gland (a slave oscillator), a full understanding of the mechanisms controlling AA-NAT gene expression in the retina by the clock is lacking. In the present study we have identified a functional E box in the first intron of the rat AA-NAT gene which is capable of mediating transcriptional upregulation via the action of a bMAL/CLOCK heterodimer. This is the first report to characterize the AA-NAT gene as a possible direct transcriptional target of the biological clock loop in a master oscillator. (C) 2000 Elsevier Science B.V. All rights reserved.