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

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...

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Autores: Abenza, Juan F., Rossetti, Leone, Mouelhi, Maleke, Burgués, Javier, Andreu, Ion, Kennedy, Keith E., Roca-Cusachs Soulere, Pere, Marco Colás, Santiago, García Ojalvo, Jordi, Trepat Guixer, Xavier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/208866
Acesso em linha:https://hdl.handle.net/2445/208866
Access Level:acceso abierto
Palavra-chave:Càncer
Ritmes circadiaris
Cèl·lules canceroses
Cancer
Circadian rhythms
Cancer cells
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spelling Mechanical control of the mammalian circadian clock via YAP/TAZ and TEADAbenza, Juan F.Rossetti, LeoneMouelhi, MalekeBurgués, JavierAndreu, IonKennedy, Keith E.Roca-Cusachs Soulere, PereMarco Colás, SantiagoGarcía Ojalvo, JordiTrepat Guixer, XavierCàncerRitmes circadiarisCèl·lules cancerosesCancerCircadian rhythmsCancer cellsAutonomous 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.Rockefeller University Press2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/208866Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1083/jcb.202209120Journal of Cell Biology, 2023, vol. 222, num.9, p. 1-20https://doi.org/10.1083/jcb.202209120cc-by (c) Abenza Juan F. et al., 2023http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2088662026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
title Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
spellingShingle Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
Abenza, Juan F.
Càncer
Ritmes circadiaris
Cèl·lules canceroses
Cancer
Circadian rhythms
Cancer cells
title_short Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
title_full Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
title_fullStr Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
title_full_unstemmed Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
title_sort Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD
dc.creator.none.fl_str_mv Abenza, Juan F.
Rossetti, Leone
Mouelhi, Maleke
Burgués, Javier
Andreu, Ion
Kennedy, Keith E.
Roca-Cusachs Soulere, Pere
Marco Colás, Santiago
García Ojalvo, Jordi
Trepat Guixer, Xavier
author Abenza, Juan F.
author_facet Abenza, Juan F.
Rossetti, Leone
Mouelhi, Maleke
Burgués, Javier
Andreu, Ion
Kennedy, Keith E.
Roca-Cusachs Soulere, Pere
Marco Colás, Santiago
García Ojalvo, Jordi
Trepat Guixer, Xavier
author_role author
author2 Rossetti, Leone
Mouelhi, Maleke
Burgués, Javier
Andreu, Ion
Kennedy, Keith E.
Roca-Cusachs Soulere, Pere
Marco Colás, Santiago
García Ojalvo, Jordi
Trepat Guixer, Xavier
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer
Ritmes circadiaris
Cèl·lules canceroses
Cancer
Circadian rhythms
Cancer cells
topic Càncer
Ritmes circadiaris
Cèl·lules canceroses
Cancer
Circadian rhythms
Cancer cells
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/208866
url https://hdl.handle.net/2445/208866
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1083/jcb.202209120
Journal of Cell Biology, 2023, vol. 222, num.9, p. 1-20
https://doi.org/10.1083/jcb.202209120
dc.rights.none.fl_str_mv cc-by (c) Abenza Juan F. et al., 2023
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Abenza Juan F. et al., 2023
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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