Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.
Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.
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DOI：
10.1016/j.cell.2018.10.042
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发表时间：
2018-12-13
期刊：
影响因子：
64.5
通讯作者：
Young RA
中科院分区：
文献类型：
--
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
基因表达受转录因子（TF）控制，TF由DNA结合结构域（DBD）和激活结构域（AD）组成。DBD已得到充分表征，但对AD影响基因激活的机制知之甚少。在这里，我们报告说，不同的广告形式相分离的冷凝物与调解人的辅活化剂。对于OCT 4和GCN 4 TF，我们表明，在体外与介体形成相分离液滴的能力和在体内激活基因的能力取决于相同的氨基酸残基。对于雌激素受体（ER），配体依赖性激活剂，我们表明，雌激素增强相分离与调解人，再次连接相分离与基因激活。这些结果表明，不同的TF可以通过其AD的相分离能力与Mediator相互作用，并且与Mediator形成缩合物参与基因激活。来自多种哺乳动物和酵母转录因子的激活结构域与介体形成相分离的缩合物以激活基因表达
Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well-characterized, but little is known about the mechanisms by which ADs effect gene activation. Here we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation. Activation domains from a diverse array of mammalian and yeast transcription factors form phase-separated condensates with mediator to activate gene expression
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