A <i>Period1</i> inducer specifically advances circadian clock in mice
Abstract
West-to-east transmeridian flights are more disruptive than east-to-west ones due to challenges in advancing the human circadian clock. Transient mammalian Period1 ( Per1 ) induction was predicted to predominantly advance the clock phase in our previous work. Here, we unravel a specific Per1 inducer, Mic-628, enabling abrupt phase advance in mouse behavioral rhythms, regardless of the timing of oral administration. Mic-628-treated mice re-entrain to phase-advanced light–dark cycles significantly faster. The direct interaction between Mic-628 and CRYPTOCHROME1 (CRY1) does not simply inhibit CRY1 repressor activity. Instead, the interaction facilitates the CLOCK-BMAL1 assembly, ensuring highly specific induction via a tandem E-box motif upstream of the Per1 promoter. Importantly, Mic-628-driven Per1 induction is repressed by PER1 itself. Mathematical modeling indicates that both the CRY1- and PER1-mediated transcriptional regulation fix the phase of Per1 induction irrespective of intake time, thereby predominantly advancing the clock phase. These findings underscore the potential of selective Per expression as a therapeutic approach for human circadian rhythm disorders.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (27)
Yoshifumi Takahata
Department of Genome Editing Research and Development Unit, Graduate School of Dentistry, University of Osaka
Yuki Kasashima
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Takuya Yoshioka
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Shusei Yashiki
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Justina Kulikauskaite
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Tomoaki Matsuura
Earth-Life Science Institute (ELSI)
Yuki Ohba
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Hideaki Hasegawa
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Naoki Yuri
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Nagisa Iwai
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Nanako Otsu
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Mikiya Kitakata
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Yuta Kitaguchi
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Haruki Furune
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Chihiro Omori
Faculty of Biological Science and Technology, Institute of Science and Engineering, Kanazawa University
Mutsumi Mukai
Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences
Yuki Komamura-Kohno
Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences
Yi-Ying Huang
Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences
Matsumi Hirose
Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences
Nobuya Koike
Laboratory of Chronogenomics, Mitsubishi Kagaku Institute of Life Sciences
Yoichi Yamada
Faculty of Biological Science and Technology, Institute of Science and Engineering, Kanazawa University
Kazuo Nakazawa
Department of Applied Chemistry and Life Science, Toyohashi University of Technology
Kumiko Ui-Tei
Department of Biological Sciences, Graduate School of Science, University of Tokyo
Yoshiyuki Sakaki
Institute of Medical Science, University of Tokyo
Rika Numano
Department of Applied Chemistry and Life Science, Toyohashi University of Technology
Koichiro Uriu
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University
Hajime Tei
Division of Biological Science and Technology, Graduate School of Natural Science and Technology, Kanazawa University