Regulation of hematopoietic cell differentiation by Mediator transcriptional coregulator complex

介体转录共调节复合体的MED1亚单位共激活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。MED1N端片段不能与GATA1相互作用，促进GATA1靶向基因转录和红系分化。GATA1的C-末端锌指结构域与MED1(1-602)相互作用的辅活化子CCAR1、可可和MED1(681-715)相互作用。CCAR1和可可协同增强GATA1介导的转录。重组的GATA1、CCAR1、COCO和MED1(1-602)在体外形成复合体，在红系分化过程中GATA1、CCAR1、COCO和MED1被招募到γ-珠蛋白启动子。因此，除了GATA1和MED1之间的直接相互作用外，可可和CCAR1似乎还将GATA1信号传递给MED1，GATA1-MED1轴的多种模式可能有助于在GATA1介导的动态平衡事件中微调GATA1的功能。

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. 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.