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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.

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