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

Masao Doi (), Hiroyuki Shimatani, Yuta Atobe, Iori Murai, Hida Hayashi, Yukari Takahashi, Jean-Michel Fustin, Yoshiaki Yamaguchi, Hiroshi Kiyonari, Nobuya Koike, Kazuhiro Yagita, Choogon Lee, Manabu Abe, Kenji Sakimura and Hitoshi Okamura ()
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Masao Doi: Kyoto University
Hiroyuki Shimatani: Kyoto University
Yuta Atobe: Kyoto University
Iori Murai: Kyoto University
Hida Hayashi: Kyoto University
Yukari Takahashi: Kyoto University
Jean-Michel Fustin: Kyoto University
Yoshiaki Yamaguchi: Kyoto University
Hiroshi Kiyonari: RIKEN Center for Biosystems Dynamics Research
Nobuya Koike: Kyoto Prefectural University of Medicine
Kazuhiro Yagita: Kyoto Prefectural University of Medicine
Choogon Lee: Florida State University
Manabu Abe: Niigata University
Kenji Sakimura: Niigata University
Hitoshi Okamura: Kyoto University

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10532-2

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