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2023-06-28

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cc-by (c) Abenza Juan F. et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/208866

Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD

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https://doi.org/10.1083/jcb.202209120

Abstract

Autonomous circadian clocks exist in nearly every mammalian cell type. These cellular clocks are subjected to a multilayered regulation sensitive to the mechanochemical cell microenvironment. Whereas the biochemical signaling that controls the cellular circadian clock is increasingly well understood, mechanisms underlying regulation by mechanical cues are largely unknown. Here we show that the fibroblast circadian clock is mechanically regulated through YAP/TAZ nuclear levels. We use high-throughput analysis of single-cell circadian rhythms and apply controlled mechanical, biochemical, and genetic perturbations to study the expression of the clock gene Rev-erbα. We observe that Rev-erbα circadian oscillations are disrupted with YAP/TAZ nuclear translocation. By targeted mutations and overexpression of YAP/TAZ, we show that this mechanobiological regulation, which also impacts core components of the clock such as Bmal1 and Cry1, depends on the binding of YAP/TAZ to the transcriptional effector TEAD. This mechanism could explain the impairment of circadian rhythms observed when YAP/TAZ activity is upregulated, as in cancer and aging.

Subject

Càncer, Ritmes circadiaris, Cèl·lules canceroses

Subject (English)

Cancer, Circadian rhythms, Cancer cells

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Articles publicats en revistes (Biomedicina)

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ABENZA, Juan F., et al. Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD. Journal of Cell Biology. 2023. Vol. 222, num. 9, pags. 1-20. ISSN 0021-9525. [consulted: 17 of August of 2026]. Available at: https://hdl.handle.net/2445/208866

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