Regulation of hematopoietic cell differentiation by Mediator transcriptional coregulator complex

介导转录共调节复合物对造血细胞分化的调节

• 批准号: 23790623
• 负责人: URAHAMA Norinaga
• 金额: $ 2.75万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790623/
• 关键词: MED1; Mediator; GATA1; CCAR1; CoCoA; メディエーター転写複合体; 赤芽球分化; K562; 転写メディエーター; MED1/TRAP220; 核内シグナル経路

The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1- and MED1-mediated transcription. An N-terminal fragment of MED1, which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation. The C-terminal zinc-finger domain of GATA1 interacts with the MED1(1-602)-interacting coactivator CCAR1, CoCoA, and MED1(681-715). CCAR1 and CoCoA synergistically enhanced GATA1-mediated transcription. Recombinant GATA1, CCAR1, CoCoA, and MED1(1-602) formed a complex in vitro, and GATA1, CCAR1, CoCoA, and MED1 were recruited to the gamma-globin promoter during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1-MED1 axis may help to fine-tune GATA1 function during GATA1-mediated homeostasis events.

介体转录辅助调节因子复合物的MED 1亚基共激活GATA 1并诱导红细胞生成。在这里，我们展示了GATA 1和MED 1介导的转录的双重机制。MED 1的N-末端片段不能与GATA 1相互作用，可增强GATA 1靶向基因转录和红细胞分化。GATA 1的C-末端锌指结构域与MED 1（1-602）相互作用辅激活因子CCAR 1、可可和MED 1（681-715）相互作用。CCAR 1和可可辅酶A协同增强GATA 1介导的转录。重组GATA 1、CCAR 1、可可辅酶A和MED 1（1-602）在体外形成复合物，在红系分化过程中，GATA 1、CCAR 1、可可辅酶A和MED 1被募集至γ-珠蛋白启动子。因此，除了GATA 1和MED 1之间的直接相互作用外，可可辅酶A和CCAR 1似乎还将GATA 1信号传递给MED 1，并且GATA 1-MED 1轴的多种模式可能有助于在GATA 1介导的稳态事件期间微调GATA 1功能。

项目成果

Mediator subunit MED1 is a T3-dependent coactivator on nTRE of the TSHβpromoter

介导亚基 MED1 是 TSHβ 启动子 nTRE 上的 T3 依赖性共激活子

• 发表时间: 2012
• 作者: K. Matsui;K. Oda;T. Hata;Sh. Mizuta;Y. Hirohata;R. Ishino;N. Urahama;R.G. Roeder;M. Ito
• 通讯作者: M. Ito

CoCoA/CCAR1 pair-mediated recruitment of Mediator complex indicates novel pathway for the function of GATA1 in erythroid differentiation

CoCoA/CCAR1 对介导的介导复合物的募集表明 GATA1 在红系分化中发挥作用的新途径

• 发表时间: 2011
• 作者: C. Kaminaga;S. Mizuta;T. Minami;K. Oda;H. Fujita;K. Matsui;R. Ishino;Sumitomo;N. Urahama;M. Ito
• 通讯作者: M. Ito

GATA1特異的転写共役因子MED1を介する赤芽球分化における核内シグナル副経路の存在

GATA1特异性转录共激活因子MED1介导的成红细胞分化中替代核信号通路的存在

• 发表时间: 2011
• 作者: 水田駿平;南智也;神永千尋;織田華澄;藤田陽加;松井啓治;石野瑠璃;住友明子;浦浜憲永;伊藤光宏
• 通讯作者: 伊藤光宏

CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function.

• DOI: 10.1111/gtc.12104
• 发表时间: 2014-01
• 期刊: Genes to cells : devoted to molecular & cellular mechanisms
• 作者: Mizuta S;Minami T;Fujita H;Kaminaga C;Matsui K;Ishino R;Fujita A;Oda K;Kawai A;Hasegawa N;Urahama N;Roeder RG;Ito M
• 通讯作者: Ito M

CCAR1/CoCoA-mediated Mediator recruitment indicates novel pathway for GATA1 action in erythropoiesis.

CCAR1/CoCoA 介导的介质招募表明 GATA1 在红细胞生成中发挥作用的新途径。

• 发表时间: 2012
• 作者: Shumpei Mizuta;Chihiro Kaminaga;Haruka Fujita;Keiji Matsui;Ruri Ishino;Kasumi Oda;Azusa Fujita;Nana Kubota;Norinaga Urahama;Mitsuhiro Ito
• 通讯作者: Mitsuhiro Ito