| Project/Area Number |
13671029
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Saitama Medical University |
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Principal Investigator |
IKEDA Masaaki SAITAMA MEDICAL SCHOOL, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (80232198)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Kazunori SAITAMA MEDICAL SHOOL, MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (20158497)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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