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Concerted localization-resets precede YAP-dependent transcription

Author

Listed:
  • J. Matthew Franklin

    (Stanford University
    Stanford University
    Stanford University
    Stanford Cancer Institute)

  • Rajarshi P. Ghosh

    (Stanford University
    Stanford University
    Stanford University
    Stanford Cancer Institute)

  • Quanming Shi

    (Stanford University
    Stanford University
    Stanford University
    Stanford Cancer Institute)

  • Michael P. Reddick

    (Stanford University
    Stanford University
    Stanford University
    Stanford Cancer Institute)

  • Jan T. Liphardt

    (Stanford University
    Stanford University
    Stanford University
    Stanford Cancer Institute)

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.

Suggested Citation

  • J. Matthew Franklin & Rajarshi P. Ghosh & Quanming Shi & Michael P. Reddick & Jan T. Liphardt, 2020. "Concerted localization-resets precede YAP-dependent transcription," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18368-x
    DOI: 10.1038/s41467-020-18368-x
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    Cited by:

    1. Kirstin Meyer & Nicholas C. Lammers & Lukasz J. Bugaj & Hernan G. Garcia & Orion D. Weiner, 2023. "Optogenetic control of YAP reveals a dynamic communication code for stem cell fate and proliferation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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