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BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis
- Welz, Patrick-Simon;
- Zinna, Valentina M;
- Symeonidi, Aikaterini;
- Koronowski, Kevin B;
- Kinouchi, Kenichiro;
- Smith, Jacob G;
- Guillén, Inés Marín;
- Castellanos, Andrés;
- Furrow, Stephen;
- Aragón, Ferrán;
- Crainiciuc, Georgiana;
- Prats, Neus;
- Caballero, Juan Martín;
- Hidalgo, Andrés;
- Sassone-Corsi, Paolo;
- Benitah, Salvador Aznar
- et al.
Published Web Location
https://doi.org/10.1016/j.cell.2019.05.009Abstract
Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1-dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond independently to environmental signals, or require interactions with each other to do so? We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues. Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness. Importantly, tissue-autonomous Bmal1 partially sustains homeostasis in otherwise arrhythmic and prematurely aging animals. Our results therefore support a two-branched model for the daily synchronization of tissues: an autonomous response branch, whereby light entrains circadian clocks without any commitment of other Bmal1-dependent clocks, and a memory branch using other Bmal1-dependent clocks to "remember" time in the absence of external cues.
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