| Project/Area Number |
18390093
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
TAKUMI Toru Osaka Bioscience Institute, Neuroscience, Lab Head (00222092)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Atsuko Osaka Bioscience Institute, Neuroscience, 研究員 (70390812)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | gene / gene expression / behavior / physiology |
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| Research Abstract |
The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two bHLH-PAS domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxed or E-box-like sequences have also been reported to be necessary for circadian oscillation. We found a new cis-element required for cell-autonomous circadian transcription of cock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrated that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verified that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Thus, the direct repeat of the E-box-like elements is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.
On the other hand, we developed in vivo monitoring of circadian timing in freely moving mice by recording multi-unit neural activity (MIJA). Suprachiasmatic nucleus (SCN), the mammalian circadian center, neural activity is tightly coupled to environmental photic input and anticorrelated with MUA rhythm in the subparaventricular zone (SPZ). In Clock mutant mice exhibiting attenuated circadian locomotor rhythmicity, MUA rhythmicity in the SCN and SPZ is similarly blunted. These results suggest that the SPZ plays a functional role in relaying circadian and photic signals to centers involved in generating behavioral activity.
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