| Project/Area Number |
08680853
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE |
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Principal Investigator |
OHSAKO Shunji TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE,DPARTMENT OF CELL BIOLOGY,STAFF SCIENTIST, 神経細胞生物学研究部門, 主事研究員 (50152103)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAMATSU Yoshiki TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE,DPARTMENT OF CELL BIOLOGY,STAFF SC, 神経細胞生物学研究部門, 主事研究員 (50250204)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Neural development / Helix-Loop-Helix / Transcription / Repressor / Corepressor / Activator / WRPW motif / Drosophila / ヘリックス・ループ・へリックス / 転写調節 / Schneider細胞 |
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| Research Abstract |
To understand the molecular mechanisms of neural cell fate determination, we are studying on the mechanism of action of the Hairy-related basec helix-loop-helix (bHLH) repressor proteins in neural development. We have previously shown that the Hairy bHLH protein does bind to a single CACGCG site in the achaete proneural gene, represses achaete transcription and as a consequence blocks ectopic sensory organ formation in Drosophila. In this study, we addressed how the Hairy bHLH protein represses transcription by binding to a target gene. Using transient transfection assays, we have demonstrated that the carboxyo-terminal WRPW motif of the Hairy-related bHLH repressors acts as a 4-amino-acid transcription repression domain and a protein interaction domain with the Grucho-related corepressors. We have also shown that the Gruocho-related proteins actively repress transcription when directly bound to a target gene promoter and identified a novel, highly conserved transcriptional repression domain in these proteins. Moreover, using transgenic flies, we have clearly shown that the WRPW motif of the Hairy-related repressors and the amino-terminal transcriptional repression domains of the Groucho-related corepressors can function as repressors of Drosophila sensory organ formation by targeting to the achaete gene through a heterologous protein Gal4. These results strongly support a model that the Hairy bHLH protein bound to the distally located CACGCG site actively represses achaete transcription by recruitment of the Groucho corepressor protein via the WRPW motif to the achaete promoter to prevent sensory organ formation in the incorrect locations in Drosophila.
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