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

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• dc.contributor.author Abenza, Juan F.
• dc.contributor.author Rossetti, Leone
• dc.contributor.author Mouelhi, Malèke
• dc.contributor.author Burgués, Javier
• dc.contributor.author Andreu, Ion
• dc.contributor.author Kennedy, Keith Endres
• dc.contributor.author Roca-Cusachs, Pere
• dc.contributor.author Marco, Santiago
• dc.contributor.author García Ojalvo, Jordi
• dc.contributor.author Trepat, Xavier
• dc.date.accessioned 2024-03-20T13:47:43Z
• dc.date.available 2024-03-20T13:47:43Z
• dc.date.issued 2023
• dc.description.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.
• dc.description.sponsorship This paper was funded by The Generalitat de Catalunya (AGAUR SGR-2017-01602 to X. Trepat, AGAUR Beatriu de Pinós 2014 BP-B 00105 to J.F. Abenza, the CERCA Programme, and “ICREA Academia” awards to P. Roca-Cusachs and J. García-Ojalvo); Spanish Ministry for Science and Innovation MICINN/FEDER (PGC2018-099645-B-I00 to X. Trepat, BFU2016-79916-P and PID2019-110298GB-I00 to P. Roca-Cusachs, and PID2021-127311NB-I00 to J. García-Ojalvo); European Research Council (Adv-883739 to X. Trepat); Fundació la Marató de TV3 (project 201903-30-31-32 to X. Trepat); European Commission (H2020-FETPROACT-01-2016-731957 to P. Roca-Cusachs and X. Trepat, H2020 Marie Sklodowska-Curie Actions MECHADIAN - IF/750557 to J.F. Abenza); La Caixa Foundation (LCF/PR/HR20/52400004 to P. Roca-Cusachs and X. Trepat); Institute for Bioengineering of Catalonia is recipient of a Severo Ochoa Award of Excellence from the Ministry of Economy and Competitiveness. DCEXS-UPF is recipient of a Maria de Maeztu Award of Excellence from the Ministry of Economy and Competitiveness.
• dc.format.mimetype application/pdf
• dc.identifier.citation Abenza 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.202209120
• dc.identifier.doi http://dx.doi.org/10.1083/jcb.202209120
• dc.identifier.issn 0021-9525
• dc.identifier.uri http://hdl.handle.net/10230/59506
• dc.language.iso eng
• dc.publisher Rockefeller University Press
• dc.relation.ispartof J Cell Biol. 2023 Sep 4;222(9):e202209120
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/731957
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-099645-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-79916-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110298GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-127311NB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/750557
• dc.rights © 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/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/4.0/
• dc.subject.keyword Cell signaling
• dc.subject.keyword Genetics
• dc.subject.keyword Physiology
• dc.subject.keyword Protein homeostasis
• dc.title Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion