| Project/Area Number |
14002011
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
ISHII Shunsuke RIKEN, Molecular Genetics Laboratory, Chief Scientist, 石井分子遺伝学研究室, 主任研究員 (00124785)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Nobukazu RIKEN, Molecular Genetics Laboratory, Special postdoctoral researcher, 石井分子遺伝学研究室, 基礎科学特別研究員 (80391978)
ISHIDAO Takefumi RIKEN, Molecular Genetics Laboratory, Collaborative researcher, 石井分子遺伝学研究室, 協力研究員 (20391857)
品川 敏恵 独立行政法人理化学研究所, 石井分子遺伝子学研究室, 研究員 (70344041)
古倉 健嗣 独立行政法人理化学研究所, 分子遺伝学研究室, 基礎科学特別研究 (30344039)
田中 康範 独立行政法人理化学研究所, 分子遺伝学研究室, 研究員 (80311348)
高木 豪 理化学研究所, 分子遺伝学研究室, 研究員 (70300879)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥594,100,000 (Direct Cost: ¥457,000,000、Indirect Cost: ¥137,100,000)
Fiscal Year 2006: ¥120,900,000 (Direct Cost: ¥93,000,000、Indirect Cost: ¥27,900,000)
Fiscal Year 2005: ¥120,900,000 (Direct Cost: ¥93,000,000、Indirect Cost: ¥27,900,000)
Fiscal Year 2004: ¥120,900,000 (Direct Cost: ¥93,000,000、Indirect Cost: ¥27,900,000)
Fiscal Year 2003: ¥110,500,000 (Direct Cost: ¥85,000,000、Indirect Cost: ¥25,500,000)
Fiscal Year 2002: ¥120,900,000 (Direct Cost: ¥93,000,000、Indirect Cost: ¥27,900,000)
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| Keywords | Gene expression / Transcription control / Transcription mediators / Transcription factors / Development / Mice / Drosophila / Structure |
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| Research Abstract |
To understand the mediator-dependent transcriptional control, the following 4 aspects of research were performed.
1) Switching between coactivators and corepressrs on the transcription factor: We found that transcription factor c-Myb competitively binds to the cocativator CBP and to multiple corespressors, including Ski.
Further, p53 binds to and recruit corepressor mSin3A to c-Myb. leading to repression of transcription of the cell-cycle regulator genes.
2) Regulation of mediators by specific signaling: We demonstrated that Wnt signal activates the HIPK2 kinase, which acts as a corepressor, and leads to binding of NLK kinase to c-Myb. NLK directly phosphorylates c-Myb and its proteasome-dependent degradation. In the case of A-Myb, HIPK2 recruites histome methyltransferase to A-Myb, but does not induce the A-Myb degradation.
3) Physiological role of mediators : By analysis of Ski knockout mice, we found that Ski acts as a corepressor of Gli3, which functions in the hedgehog signaing pathway. We also found that the Shn-2 knockout mice have the defective adipocyte differentiation. Shn-2 acts as a platform protein and mediates the interaction between coactivators and multiple transcription factors to synergistically induce transcription of the PPAR□2 gene, which is essential for the adipocyte differentiation.
4) Analysis of the nuclear architecture in transcriptional control : We identified the factor that regulates the subnuclear localization of transcription factors, which play an important role in development.
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