CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function.
CCAR1/CoCoA pair-mediated recruitment of the Mediator defines a novel pathway for GATA1 function.
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DOI：
10.1111/gtc.12104
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Ito M
中科院分区：
文献类型：
--
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
介体转录共调节复合物的 MED1 亚基共同激活 GATA1 并诱导红细胞生成。在这里，我们展示了 GATA1 和 MED1 介导的转录的双重机制。 K562 红白血病细胞中的 MED1 表达水平与 GATA1 靶向基因转录和红系分化水平平行。 MED1 的 N 端片段 MED1(1–602) 无法与 GATA1 相互作用，增强了 GATA1 靶向基因转录和红系分化，并将 MED1(1–602) 引入 Med1−/− 小鼠胚胎成纤维细胞 (MEF) 部分挽救了 GATA1 介导的转录。 GATA1 的 C 端锌指结构域与 MED1(1–602) 相互作用的共激活因子 CCAR1、CoCoA 和 MED1(681–715) 相互作用。 CCAR1 和 CoCoA 协同增强 MEF 中 GATA1 介导的 γ-珠蛋白启动子转录。重组GATA1、CCAR1、CoCoA和MED1(1-602)在体外形成复合物，并且GATA1、CCAR1、CoCoA和MED1在红系分化过程中被招募到K562细胞中的γ-珠蛋白启动子。因此，除了GATA1和MED1之间的直接相互作用外，CoCoA和CCAR1似乎还将GATA1信号传递给MED1，并且GATA1-MED1轴的多种模式可能有助于在GATA1介导的稳态事件期间微调GATA1功能。
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. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1-targeted gene transcription and erythroid differentiation. An N-terminal fragment of MED1, MED1(1–602), which is incapable of interacting with GATA1, enhanced GATA1-targeted gene transcription and erythroid differentiation, and introduction of MED1(1–602) into Med1−/− mouse embryonic fibroblasts (MEFs) partially rescued GATA1-mediated transcription. 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 from the γ-globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA, and MED1(1–602) formed a complex in vitro, and GATA1, CCAR1, CoCoA, and MED1 were recruited to the γ-globin promoter in K562 cells 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.
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影响因子：
7.3
作者：
Chen, Wei;Roeder, Robert G.
通讯作者：
Roeder, Robert G.
影响因子：
4.8
作者：
Lam, LT;Ronchini, C;Bresnick, EH
通讯作者：
Bresnick, EH
影响因子：
20.3
作者：
LOZZIO, CB;LOZZIO, BB
通讯作者：
LOZZIO, BB
DOI：
10.1084/jem.20102260
发表时间：
2010-11-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kerenyi MA;Orkin SH
通讯作者：
Orkin SH
影响因子：
64.8
作者：
Ge, K;Guermah, M;Roeder, RG
通讯作者：
Roeder, RG