Abenza, Juan F.Rossetti, LeoneMouelhi, MalèkeBurgués, JavierAndreu, IonKennedy, Keith EndresRoca-Cusachs, PereMarco, SantiagoGarcía Ojalvo, JordiTrepat, Xavier2024-03-202024-03-202023Abenza JF, Rossetti L, Mouelhi M, Burgués J, Andreu I, Kennedy K, et al. Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD. J Cell Biol. 2023 Sep 4;222(9):e202209120. DOI: 10.1083/jcb.2022091200021-9525http://hdl.handle.net/10230/59506Autonomous 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.application/pdfeng© 2023 Abenza et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.1083/jcb.202209120Cell signalingGeneticsPhysiologyProtein homeostasisinfo:eu-repo/semantics/openAccess