Concerted localization-resets precede YAP-dependent transcription
Concerted localization-resets precede YAP-dependent transcription
复制标题
协调的定位重置先于YAP依赖的转录
DOI：
10.1038/s41467-020-18368-x
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发表时间：
2020-09-11
影响因子：
16.6
通讯作者：
Liphardt, Jan T.
中科院分区：
文献类型：
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作者：
Franklin, J. Matthew;Ghosh, Rajarshi P.;Liphardt, Jan T.
Yes相关蛋白1（雅普）是一种转录调节因子，在机械信号转导、器官大小调控和再生中起重要作用。在这里，使用先进的工具，实时可视化的本地雅普和靶基因的转录动力学，我们表明，一个周期的快速外流的细胞核雅普的细胞质，然后快速返回到细胞核（“定位重置”）激活雅普靶基因。这些“重置”是由钙信号传导、肌动球蛋白收缩性的调节或有丝分裂诱导的。使用起始转录报告基因敲入的雅普靶基因，我们显示了这些重置和下游转录之间的严格关联。致癌性转化的细胞系缺乏定位重置，而是显示出雅普的核质穿梭速率显著升高，表明从基于区室化的控制中逃脱。单细胞定位和转录痕迹表明，雅普活性不是一个简单的线性函数的核富集和点的转录激活模型的基础上的核质交换性能的雅普。
Yes-associated protein 1 (YAP) is a transcriptional regulator with critical roles in mechan-otransduction, organ size control, and regeneration. Here, using advanced tools for real-time visualization of native YAP and target gene transcription dynamics, we show that a cycle of fast exodus of nuclear YAP to the cytoplasm followed by fast reentry to the nucleus ("localization-resets") activates YAP target genes. These "resets" are induced by calcium signaling, modulation of actomyosin contractility, or mitosis. Using nascent-transcription reporter knock-ins of YAP target genes, we show a strict association between these resets and downstream transcription. Oncogenically-transformed cell lines lack localization-resets and instead show dramatically elevated rates of nucleocytoplasmic shuttling of YAP, suggesting an escape from compartmentalization-based control. The single-cell localization and transcription traces suggest that YAP activity is not a simple linear function of nuclear enrichment and point to a model of transcriptional activation based on nucleocytoplasmic exchange properties of YAP.