Research on HPA axis and clock genes.

HPA轴和时钟基因的研究。

• 批准号: 13671029
• 负责人: IKEDA Masaaki
• 金额: $ 2.18万
• 依托单位: Saitama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671029/
• 关键词: clock gene; HPA axis; circadian rhythm; BMAL1; transcription factor; transcriptional regulation; promoter; orphan nuclear receptor; 概日リズム; HPA axis; 視床下部; Bmal1; Clock; HPAアキシス; CRY1; CLOCK; PER2; Inter-activationg Loop

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.

在哺乳动物中，生物钟是由下丘脑中大脑区域的核上核（SCN）控制的。光通过视网膜 - 高层丘脑（RHT）将昼夜节律设置为24小时的浅色循环。输出基因的大部分转录都是由BMAL1：作用在其启动子区域的电子箱上的时钟介导的，表明BMAL1和时钟基因的转录水平的重要性。为了研究BMAL1基因的转录控制，我们使用BMAL1启动子构建体使用了荧光素酶报告基因测定法，以找到调节BMAL1转录的因素。这表明RORα，RORβ和RORγ增强了BMAL1启动子构建体的报告活性，并通过RERBβ通过ROR反应元件（ROR-RE）抑制了Rev-ERBβ。 RORα是BMAL1转录的最潜在活化剂。因此，我们假设在SCN中表达的ROR和REV-ERB家族的成员通过ROR-RE结合了BMAL1启动子，并且由ROR和Rev-ERB家族成员引起的BMAL1激活水平主要取决于其招募到结合位点的招募。

项目成果

Ikeda M, Honma S, Abe H 他: "Molecular cloning and characterization of the clock gene Bmal1, in Zeitgebers, entrainment and masking of the circadian system"Hokkaido University Press, Sapporo, Japan. 5 (2001)

Ikeda M、Honma S、Abe H 等人：“时钟基因 Bmal1 的分子克隆和表征，Zeitgebers、昼夜节律系统的夹带和掩蔽”北海道大学出版社，札幌，日本 5 (2001)。

Abe H, Honma S, Namihira M, Masubuchi S, Ikeda M, Ebihara S, Honma K: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol.Brain Res. 87. 92-99 (2001)

Abe H、Honma S、Namihira M、Masubuchi S、Ikeda M、Ebihara S、Honma K：“CS 小鼠胸腺分裂期间视交叉上粘核和大脑其他区域的时钟基因表达”Mol.Brain Res。

池田正明: "PAS因子の構造と機能"神経研究の進歩. 45. 742-754 (2001)

Masaaki Ikeda：“PAS 因子的结构和功能”神经学研究进展 45. 742-754 (2001)。

Abe H, Honma S, Namihira M 他: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol Brain Res. 87. 92-99 (2001)

Abe H、Honma S、Namihira M 等：“CS 小鼠胸腺分裂过程中视交叉上粘和大脑其他区域的时钟基因表达”Mol Brain Res. 87. 92-99 (2001)

Abe H, Honma S, Namihira M, Masubuchi S, Ikeda_M, Ebihara S, Honma K: "Clock gene expressions in the suprachiasmatic mucleus and other areas of the brain during thythm splitting in CS mice"Mol.Brain Res. 87. 92-99 (2001)

Abe H、Honma S、Namihira M、Masubuchi S、Ikeda_M、Ebihara S、Honma K：“CS 小鼠胸腺分裂期间视交叉上粘核和大脑其他区域的时钟基因表达”Mol.Brain Res。