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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / metabolism
  • ARNTL Transcription Factors / physiology*
  • Animals
  • CLOCK Proteins / metabolism
  • Circadian Clocks / genetics*
  • Circadian Clocks / physiology
  • Circadian Rhythm / genetics
  • Feeding Behavior / physiology
  • Female
  • Homeostasis
  • Light
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Organ Specificity / physiology
  • Photoperiod
  • Suprachiasmatic Nucleus / metabolism

Substances

  • ARNTL Transcription Factors
  • CLOCK Proteins