2006 Fiscal Year Final Research Report Summary
Transcriptional control by mediators and their physiological significance
| 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)
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| Project Period (FY) |
2002 – 2006
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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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