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，生物钟由视交叉上核 (SCN) 控制，视交叉上核是下丘脑的大脑区域，光通过视网膜下丘脑束 (RHT) 将昼夜节律设置为 24 小时明暗周期。输出基因的大部分转录是由 BMAL1 介导的：CLOCK 作用于其启动子区域的 E-box，这表明 Bmal1 和 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 启动子构建体进行荧光素酶报告基因测定，以寻找调节 Bmal1 转录的因子，这表明 RORα、RORβ 和 RORγ 增强了 Bmal1 启动子构建体的报告基因活性。 ，并通过 ROR 响应元件 (ROR-RE) 被 Rev-Erbβ 抑制，因此，我们发现 RORα 是 Bmal1 转录最有效的激活剂。假设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激活水平主要由其总和决定他们被招募到结合位点。

项目成果

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。

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)。

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。