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

First Author  Doi M Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  2563
PubMed ID  31189882 Mgi Jnum  J:276909
Mgi Id  MGI:6323703 Doi  10.1038/s41467-019-10532-2
Citation  Doi M, et al. (2019) Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity. Nat Commun 10(1):2563
abstractText  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.
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