Concerted localization-resets precede YAP-dependent transcription

J. Matthew Franklin, Rajarshi P. Ghosh (), Quanming Shi, Michael P. Reddick and Jan T. Liphardt ()
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J. Matthew Franklin: Stanford University
Rajarshi P. Ghosh: Stanford University
Quanming Shi: Stanford University
Michael P. Reddick: Stanford University
Jan T. Liphardt: Stanford University

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract Yes-associated protein 1 (YAP) is a transcriptional regulator with critical roles in mechanotransduction, 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.

Date: 2020
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DOI: 10.1038/s41467-020-18368-x

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