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

• Doi, Masao

• Shimatani, Hiroyuki

• Atobe, Yuta

• Murai, Iori

• Hayashi, Hida

• Takahashi, Yukari

• Fustin, Jean-Michel

• Yamaguchi, Yoshiaki

• Kiyonari, Hiroshi

• Koike, Nobuya

• Yagita, Kazuhiro

• Lee, Choogon

• Abe, Manabu

• Sakimura, Kenji

• Okamura, Hitoshi

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.

Journal

• Nature Communications

  Nature Communications 10 2563-, 2019-06-12

  Springer Science and Business Media LLC

Keywords

• Circadian rhythms
• Gene regulation

Details

• CRID: 1050282677513048192
• NII Article ID: 120006644061
• ISSN: 20411723
• DOI: 10.1038/s41467-019-10532-2
• HANDLE: 2433/241740
• Web Site: https://www.nature.com/articles/s41467-019-10532-2.pdf
• Web Site: https://www.nature.com/articles/s41467-019-10532-2
• Text Lang: en
• Article Type: journal article
• Data Source:
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  • CiNii Articles
  • KAKEN