Research on HPA axis and clock genes.

在哺乳动物中，生物钟是由视交叉上核(SCN)控制的，SCN是大脑下丘脑的一个区域。光通过视网膜-下丘脑束(RHT)将昼夜节律设定为24小时的明暗循环。输出基因的大部分转录是由BMAL1：Clock作用于其启动子区域的E盒而介导的，这表明了BMal1和Clock基因转录水平的重要性。为了研究BMal1基因的转录调控，我们使用了一种使用BMal1启动子构建的荧光素酶报告基因的方法来寻找调控BMal1转录的因子。这表明BMal1启动子的报告活性被RoRα、RoRβ和RoRγ增强，而被REV-Erbβ通过RoR反应元件(RoR-RE)抑制。RoRα是BMal1转录的最强激活剂。因此，我们推测在SCN中表达的ROR和Rev-Erb家族成员通过ROR-RE与BMal1启动子结合，并且ROR和Rev-Erb家族成员引起的BMal1激活水平主要由他们在结合位点上的招募之和决定。

In mammals, the biological clock is controlled from the suprachiasmatic nucleus (SCN), an area of the brain in the hypothalamus. Light sets the circadian rhythm via the retino-hypothalamic tract (RHT) to a 24-hour light-dark cycle. Much of the transcription of output genes is mediated by BMAL1 : CLOCK acting on E-boxes in their promoter regions, indicating the importance of the level of transcription of the Bmal1 and Clock genes. To investigate the transcriptional control of Bmal1 genes, we used a luciferase reporter assay using Bmal1 promoter constructs to find factors that regulate Bmal1 transcription. This revealed that the reporter activity of the Bmal1 promoter constructs was enhanced by RORα, RORβ, and RORγ, and was inhibited by Rev-Erbβ via ROR-response elements(ROR-RE). RORα was the most potent activator of Bmal1 transcription. Therefore, we postulate that members of the ROR and Rev-Erb family expressed in the SCN bind to the Bmal1 promoter via ROR-RE, and that the level of Bmal1 activation caused by the members of the ROR and Rev-Erb family is determined mainly by the sum of their recruitment to the binding sites.