Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression.,Nature Cell Biology

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Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-03-23 , DOI: 10.1038/s41556-020-0485-0
Yi Lu ₁ , Tiantian Wu _{1,

2} , Orit Gutman ₃ , Huasong Lu ₁ , Qiang Zhou ₁ , Yoav I Henis ₃ , Kunxin Luo ₁

Affiliation

TAZ promotes growth, development and tumorigenesis by regulating the expression of target genes. However, the manner in which TAZ orchestrates the transcriptional responses is poorly defined. Here we demonstrate that TAZ forms nuclear condensates through liquid-liquid phase separation to compartmentalize its DNA-binding cofactor TEAD4, coactivators BRD4 and MED1, and the transcription elongation factor CDK9 for transcription. TAZ forms phase-separated droplets in vitro and liquid-like nuclear condensates in vivo, and this ability is negatively regulated by Hippo signalling through LATS-mediated phosphorylation and is mediated by the coiled-coil (CC) domain. Deletion of the TAZ CC domain or substitution with the YAP CC domain prevents the phase separation of TAZ and its ability to induce the expression of TAZ-specific target genes. Thus, we identify a mechanism of transcriptional activation by TAZ and demonstrate that pathway-specific transcription factors also engage the phase-separation mechanism for efficient and specific transcriptional activation.

中文翻译：

TAZ 的相分离分隔转录机制以促进基因表达。

TAZ 通过调节靶基因的表达来促进生长、发育和肿瘤发生。然而，TAZ 协调转录反应的方式尚不清楚。在这里，我们证明 TAZ 通过液-液相分离形成核凝聚物，将其 DNA 结合辅因子 TEAD4、共激活子 BRD4 和 MED1 以及转录延伸因子 CDK9 区分开来进行转录。 TAZ 在体外形成相分离的液滴，在体内形成液体样核凝聚物，这种能力通过 LATS 介导的磷酸化受到 Hippo 信号的负调控，并由卷曲螺旋 (CC) 结构域介导。删除 TAZ CC 结构域或替换为 YAP CC 结构域可防止 TAZ 的相分离及其诱导 TAZ 特异性靶基因表达的能力。因此，我们确定了 TAZ 转录激活的机制，并证明途径特异性转录因子也参与相分离机制，以实现有效和特异性的转录激活。

更新日期：2020-04-24

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