| Project/Area Number |
09277102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas (A)
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| Allocation Type | Single-year Grants |
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| Research Institution | Tohoku University |
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Principal Investigator |
FUJII-KURIYAMA Yoshiaki Graduate School of Life Sciences, Tohoku University Professor, 大学院・生命科学研究科, 教授 (00098146)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Masatoshi Medical Research Institute, Tokyo Medical and Dental University, Professor, 難治疾患研究所, 教授 (10208423)
KATO Shigeaki Institute of Molecular and Cellular Biosciences, The University of Tokyo, Professor, 分子細胞生物学研究所, 教授 (60204468)
AKIRA Sizuo Research Institute for Microbial Diseases, Osaka University, Professor, 微生物研究所, 教授 (50192919)
HISATAKE Koji Deprtment of Biochemistry, Saitama Medical School, Assistant professor, 第2生化学, 助教授 (70271236)
HANDA Hirosi Frontier Collaborative Research Center, Tokyo Institute of Technology, Professor, フロンティア創造共同研究センター, 教授 (80107432)
大熊 芳明 大阪大学, 細胞生体工学センター, 助教授 (70192515)
上田 均 国立遺伝学研究所, 個体遺伝研究系, 助手 (60201349)
箱嶋 敏雄 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (00164773)
梅園 和彦 京都大学, ウイルス研究所, 教授 (50183752)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥316,000,000 (Direct Cost: ¥316,000,000)
Fiscal Year 2000: ¥76,800,000 (Direct Cost: ¥76,800,000)
Fiscal Year 1999: ¥81,200,000 (Direct Cost: ¥81,200,000)
Fiscal Year 1998: ¥74,000,000 (Direct Cost: ¥74,000,000)
Fiscal Year 1997: ¥84,000,000 (Direct Cost: ¥84,000,000)
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| Keywords | transcription factor / transcriptional cofactor / inter-transcriptional interaction / functional mechanism / transcription initiation / transfer extension reaction / reorganization / transfer activation / 転写開始複合体 / リン酸化 / スプライシング / DNA結合能 / 相互作用 / TFIIH / TFIIE / TFIID / コアクチベーター / DSIF / Ah受容体 / STAT3 / CREB / 基本転写装置 / コアクチベータ- / TF II D / TF II E / TF II H / 転写調節因子 / ノックアウトマウス |
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| Research Abstract |
The purpose of this research group is to elucidate the molecular mechanism of interaction between transcription factors including transcription coordinators finally leading to the expression of specific genes. TFIIH composed of 9 subemits was successfully reconstituted from the recombinantly expressed subunit proteins in a baculovirus system. This system provides good an excellent tool for investigating the function of these individual subunits in the transcription complex and revealed that the helicase activity of ERCC3 plays and essential role of promotor escape in the transcription initiation. Subsequent to the transcription initiation, the transcription reaction was elucidated to be precisely regulated in positive and negative fashions by sing DSIF and NELF as negative factors, and pTEFb and FACT as positive factors. Mutation in the C-terminal region a subunit, p160 of DSIF was found to cause abberant neural development of zebrafish. It has been further clarified that CBP which functions as a coactivator to a variety of transcription factors also plays a coactivator or to the transcription factors, GLI3, AhR/Arnt, HIF-12 and IFR3. A complex CBP with β-catenine was found to localize at the PML region and β-catenine in hybrid the transcription activity of p53 by isolating CBP. By the two-hybrid methods, additional coactivators, MBF1, UTF1 and p68/p72 have been isolated for the transcription factors, FTZ-F1, RAR and ER α,β and their primary structures and functions have been investigated extensively. Functional analyses of transcription factors such as STAT3, AhR, VDR and many other have been extensively investigated by the gene-targeting technology.
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