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Title: Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity
Authors: 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
Author's alias: 土居, 雅夫
嶋谷, 寛之
跡部, 裕太
村井, 伊織
林, 煕達
高橋, ゆかり
Fustin, Jean-Michel
山口, 賀章
清成, 寛
小池, 宜也
八木田, 和弘
Lee, Choogon
阿部, 学
崎村, 建司
岡村, 均
Keywords: Circadian rhythms
Gene regulation
Issue Date: 12-Jun-2019
Publisher: Springer Science and Business Media LLC
Journal title: Nature Communications
Volume: 10
Thesis number: 2563
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.
Description: 体内リズムの発現に必要なDNAのスイッチを発見 --蛋白質をコードしないノンコーディング領域のDNA配列が活躍--. 京都大学プレスリリース. 2019-06-12.
Rights: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/241740
DOI(Published Version): 10.1038/s41467-019-10532-2
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190612_1.html
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