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Cell. 2019 May 30;177(6):1436-1447.e12. doi: 10.1016/j.cell.2019.05.009.

BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain. Electronic address: patrick.welz@irbbarcelona.org.
2
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
3
Center for Epigenetics and Metabolism, University of California, Irvine, CA 92697, USA.
4
Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
5
PCB-PRBB Animal Facilities, 08028 Barcelona, Spain.
6
Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain; Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336 Munich, Germany.
7
Center for Epigenetics and Metabolism, University of California, Irvine, CA 92697, USA. Electronic address: psc@uci.edu.
8
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; ICREA, Catalan Institution for Research and Advanced Studies, 08010 Barcelona, Spain. Electronic address: salvador.aznar-benitah@irbbarcelona.org.

Abstract

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.

PMID:
31150620
DOI:
10.1016/j.cell.2019.05.009

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