Transcriptional control by mediators and their physiological significance

介质的转录控制及其生理意义

• 批准号: 14002011
• 负责人: ISHII Shunsuke
• 金额: $ 380.22万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14002011/
• 关键词: Gene expression; Transcription control; Transcription mediators; Transcription factors; Development; Mice; Drosophila; Structure

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.

为了了解中介依赖性的转录控制，进行了以下4个研究。1）D Corepressrs对转录因子：我们发现转录因子C-MYB竞争性地结合了Cocativator CBP和Toltipr Essors，包括SKI.FURTHER， p53通过特定的信号结合并募集了c-myb。 HIPK2募集组织甲基转移酶至A-MYB，但不会诱导A-MYB降解。3）介体的生理角色：通过发现SKI充当Gli3 Uncle Hedge Hedgehog Signaint的核心压力。脂肪细胞有缺陷的因素，诱导PPAR的转录□2基因，这对于脂肪细胞的区分至关重要。4）转录控制中的r架构：我们确定了转录因子的亚核化。

项目成果

Generation of Ski-knock down mice by expressing a long double-strand RNA from an RNA polynerase II promoter.

通过表达来自 RNA 聚合酶 II 启动子的长双链 RNA，生成 Ski-knock down 小鼠。

• 发表时间: 2003
• 期刊: Genes Dev. 17
• 作者: Shinagawa;T. et al.
• 通讯作者: T. et al.

The Ski-binding protein C184M negatively regulate TGF- β signaling by sequestering the Smad proteins to cytoplasm.

Ski 结合蛋白 C184M 通过将 Smad 蛋白隔离在细胞质中来负向调节 TGF-β 信号传导。

• 发表时间: 2003
• 期刊: J. Biol. Chem. 278
• 作者: Kokura;K. et al.
• 通讯作者: K. et al.

Dai, P.et al.: "Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3"Genes & Development. 16. 2843-2848 (2002)

Dai, P.et al.：“Ski 参与 Gli3 阻遏物和全长形式的转录调控”基因

Mechanism of c-Myb-C/EBPβ cooperation from distantly separated sites on a promoter.

启动子上相距较远的位点的 c-Myb-C/EBPβ 合作机制。

• 发表时间: 2002
• 期刊: Cell 108
• 作者: Tahirov;T. H. et al.
• 通讯作者: T. H. et al.

ATF-2 regulates fat metabolism in Drosophila.

ATF-2 调节果蝇的脂肪代谢。

• 发表时间: 2007
• 期刊: Mol Biol Cell 18(4)
• 作者: Okamura;T.;Shimizu;H.;Nagao;T.;Ueda;R.;Ishii;S.
• 通讯作者: S.