Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity

Nat Commun. 2019 Jun 12;10(1):2563. doi: 10.1038/s41467-019-10532-2.


Non-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E'-box cis-element in the promoter region of the core clock gene Per2. The Per2 E'-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E'-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E'-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Body Temperature / physiology
  • Cells, Cultured
  • Circadian Rhythm / genetics*
  • E-Box Elements / genetics*
  • Fibroblasts
  • Locomotion / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Period Circadian Proteins / genetics*
  • Primary Cell Culture
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / metabolism


  • Per2 protein, mouse
  • Period Circadian Proteins
  • RNA, Messenger