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Dynamical mechanism of Bmal1/Rev-erbα loop in circadian clock

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  • Li, Ying
  • Liu, Zengrong

Abstract

In mammals, the circadian clock is driven by multiple integrated transcriptional feedback loops involving three kinds of central clock-controlled elements (CCEs): E-boxes, D-boxes and ROR-elements. With the aid of CCEs, the concentrations of the active proteins are approximated by the delayed concentrations of mRNAs, which simplifies the circadian system drastically. The regulatory loop composed by BMAL1 and REV-ERB- α plays important roles in circadian clock. With delay differential equations, we gave a mathematical model of this loop and investigated its dynamical mechanisms. Specially, we theoretically provided the sufficient conditions for sustained oscillation of the loop with Hopf bifurcation theory. The total of delays determines the emergence of oscillators, which explains the crucial roles of delays in circadian clock revealed by biological experiments. Numerically, we studied the amplitude and period against the variations of delays and the degradation rates. The different sensitivities of amplitude and period on these factors provide ideas to adjust the amplitude or period of circadian oscillators.

Suggested Citation

  • Li, Ying & Liu, Zengrong, 2015. "Dynamical mechanism of Bmal1/Rev-erbα loop in circadian clock," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 430(C), pages 126-135.
    • Handle: RePEc:eee:phsmap:v:430:y:2015:i:c:p:126-135
    DOI: 10.1016/j.physa.2015.02.091
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    References listed on IDEAS

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    1. Hiroki R. Ueda & Wenbin Chen & Akihito Adachi & Hisanori Wakamatsu & Satoko Hayashi & Tomohiro Takasugi & Mamoru Nagano & Ken-ichi Nakahama & Yutaka Suzuki & Sumio Sugano & Masamitsu Iino & Yasufumi S, 2002. "A transcription factor response element for gene expression during circadian night," Nature, Nature, vol. 418(6897), pages 534-539, August.
    2. Han Cho & Xuan Zhao & Megumi Hatori & Ruth T. Yu & Grant D. Barish & Michael T. Lam & Ling-Wa Chong & Luciano DiTacchio & Annette R. Atkins & Christopher K. Glass & Christopher Liddle & Johan Auwerx &, 2012. "Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β," Nature, Nature, vol. 485(7396), pages 123-127, May.
    3. Steven M. Reppert & David R. Weaver, 2002. "Coordination of circadian timing in mammals," Nature, Nature, vol. 418(6901), pages 935-941, August.
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    1. Li, Ying & Liu, Zengrong, 2016. "Coupling mechanism in the gate and oscillator model of the SCN," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 457(C), pages 62-72.

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