Dynamical mechanism of Bmal1/Rev-erb alpha loop in circadian clock

作者：Li, Ying^*; Liu, Zengrong

来源：Physica A: Statistical Mechanics and Its Applications , 2015, 430: 126-135.

DOI：10.1016/j.physa.2015.02.091

• Mathematical model
• Hopf bifurcation
• Oscillation
• Circadian clock
• Clock-controlled element

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-alpha 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.

• 出版日期2015-7-15
• 单位上海大学; 上海海洋大学