| Project/Area Number |
16207009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATO Shigeaki The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (60204468)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEYAMA Ken-ichi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Lecturer, 分子細胞生物学研究所, 講師 (30323570)
KITAGAWA Hirochika The University of Tokyo, Institute of Molecular and Cellular Biosciences, Research Associate, 分子細胞生物学研究所, 助手 (20345234)
TAKADA Ichiro The University of Tokyo, Institute of Molecular and Cellular Biosciences, Research Associate, 分子細胞生物学研究所, 助手 (50361655)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2006: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2005: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2004: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
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| Keywords | cell type-specific complex / chromatin remodeling complex / co-legulator complex / spatio-temporal gene disraption / cre-loxP system / 染色体構造調節因子 / 遺伝子発現制御 / 転写共役因子 / 転写制御因子 / 複合体構成因子 / 染色体構造調節因子複合体 / ATPase / WINAC複合体 / DNA複製活性 / DNA修復能 / 核内受容体群 |
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| Research Abstract |
Gene expression is controlled through chromatin remodeling and histon modifications. Such chromatin structure rearrangement is conducted by a number of nuclear complexes composed of multiple subunits. In the present study, to identify and characterize the nuclear complexes to support hormone-induced transcriptional controls by nuclear receptors, a biochemical purification of complexes associating with sex steroid hormone receptors. By such biochemical screening, we could identify several complexes containing histone modifying enzymes. One of the complex was a novel complex containing histone acetyltransferase to coactivate estrogen receptor, while another complex was a histone deacetylase to corepress estrogen and androgen receptors. Moreover, we could identify a novel ubiquitin E3 ligase to degrate sex steroid receptor proteins. Previously, we had shown that activated dioxin receptor(AhR) by ligand binding coactivates unliganded sex steroid receptors in transcriptional controls through direct receptor-receptor protein interaction (Ohtake et al., Nature, 423, 545-550, 2003). However, transrepression of liganded steroid receptors by AhR was still under investigation. By biochemical purification of a complex containing AhR and sex steroid receptors, we have demonstrated that liganded AhR is ligand- dependent E3 ubiquitin ligase to degrate steroid receptors, thereby counteracting biological actions of sex steroid hormones (Ohtake et al., Nature, 446, 562-566, 2007).
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