Transcription-based circadian mechanism controls the duration of molecular clock states in response to signaling inputs

Almeida, Sofia; Chaves, Madalena; Delaunay, Franck

doi:10.1016/j.jtbi.2019.110015

Cited by 32 publications

(74 citation statements)

References 61 publications

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“…The clock model is based on transcriptional regulation and is able to recover the antiphasic relation in the oscillation of the CLOCK : BMAL1 and PER : CRY proteins [19]. We begin by dynamically reducing this model in order to obtain the smallest possible network that maintains this property.…”

Section: Methodsmentioning

confidence: 99%

“…Original parameters for both models were obtained by nonlinear optimization based on costminimization, with the use of a MATLAB function [18,19]. In order to have oscillation of both systems with periods of the same order of magnitude and consistent with values of experimental observations (namely T clock = 24 h) we scale the original parameters of both models, by multiplying those referring to rates of change by an appropriate constant.…”

Section: Methodsmentioning

confidence: 99%

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Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

2020

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The cell cycle and the circadian clock are essential cyclic cellular processes often synchronous in healthy cells. In this work, we use previously developed mathematical models of the mammalian cell cycle and circadian cellular clock in order to investigate their dynamical interactions. Firstly, we study unidirectional cell cycle → clock coupling by proposing a mechanism of mitosis promoting factor (MPF)-controlled REV-ERB α degradation. Secondly, we analyse a bidirectional coupling configuration, where we add the CLOCK : BMAL1-mediated MPF repression via the WEE1 kinase to the first system. Our simulations reproduce ratios of clock to cell cycle period in agreement with experimental observations and give predictions of the system’s synchronization state response to a variety of control parameters. Specifically, growth factors accelerate the coupled oscillators and dexamethasone (Dex) drives the system from a 1 : 1 to a 3 : 2 synchronization state. Furthermore, simulations of a Dex pulse reveal that certain time regions of pulse application drive the system from 1 : 1 to 3 : 2 synchronization while others have no effect, revealing the existence of a responsive and an irresponsive system’s phase, a result we contextualize with observations on the segregation of Dex-treated cells into two populations.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

2020

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“…The effect of changes in most of the degradation rates was opposite to the effect of changes in activating CCE parameters (figure 10a). The model published by Almeida et al [57] showed oscillations with a period of approximately 20 h. Since…”

Section: Appendix C Period Sensitivity Analyses and Tuning Of The Modelmentioning

confidence: 96%

“…We numerically simulated the ODE models with the published parameter values [57], and performed control analysis on the eight ODE model to assess the effect of parameter changes on the oscillation period (appendix C). We found that the oscillation period strongly depended on the degradation rates of REVERB, E4BP4 and DBP (figure 10).…”

Section: Different Circadian Clock Models Exhibit Self-sustained Oscimentioning

confidence: 99%

“…We found that the oscillation period strongly depended on the degradation rates of REVERB, E4BP4 and DBP (figure 10). Since the period of the ODE models was approximately 20 h [57], we tuned the degradation rate of REVERB (γ REV ) to set the period to approximately 24 h. Simulations of the three DDE model with the published parameter set yielded 24 h oscillations [31]. The time series solutions of the eight ODE and three DDE models are shown in figure 3.…”

Section: Different Circadian Clock Models Exhibit Self-sustained Oscimentioning

confidence: 99%

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Nonlinear phenomena in models of the circadian clock

Soest

Olmo

Schmal

et al. 2020

J. R. Soc. Interface.

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The mammalian circadian clock is well-known to be important for our sleep–wake cycles, as well as other daily rhythms such as temperature regulation, hormone release or feeding–fasting cycles. Under normal conditions, these daily cyclic events follow 24 h limit cycle oscillations, but under some circumstances, more complex nonlinear phenomena, such as the emergence of chaos, or the splitting of physiological dynamics into oscillations with two different periods, can be observed. These nonlinear events have been described at the organismic and tissue level, but whether they occur at the cellular level is still unknown. Our results show that period-doubling, chaos and splitting appear in different models of the mammalian circadian clock with interlocked feedback loops and in the absence of external forcing. We find that changes in the degradation of clock genes and proteins greatly alter the dynamics of the system and can induce complex nonlinear events. Our findings highlight the role of degradation rates in determining the oscillatory behaviour of clock components, and can contribute to the understanding of molecular mechanisms of circadian dysregulation.

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A scenario of unhealthy life cycle: The role of circadian rhythms in health

Chandramouli,

Basavanna,

Ningaiah

2024

Aging Medicine

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Circadian rhythms are oscillations in physiology and behavior caused by the circadian regulator. Cryptochromes, Periods, and Bmal1 are circadian clock genes that have been linked to aging and cancer. Human pathologies alter circadian clock gene expression, and transgenic rats with clock gene defects progress to cancer and age prematurely. In the growth of age‐linked pathologies and carcinogenesis, cell proliferation and genome integrity play critical roles. The relationship concerning the cell cycle regulation and circadian clock is discussed in this article. The circadian clock controls the behavior and countenance of many main cell cycle and cell cycle check‐point proteins, and cell cycle‐associated proteins, in turn, control the activity and expression of circadian clock proteins. The circadian clock can be reset by DNA disruption, providing a molecular mechanism for mutual control amid the cell cycle and the clock. This circadian clock‐dependent regulation of cell proliferation, composed with other circadian clock‐dependent physiological functions including metabolism control, genotoxic and oxidative stress response, and DNA repair, unlocks new avenues for studying the processes of aging and carcinogenesis.

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Transcription-based circadian mechanism controls the duration of molecular clock states in response to signaling inputs

Cited by 32 publications

References 61 publications

Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

Control of synchronization ratios in clock/cell cycle coupling by growth factors and glucocorticoids

Nonlinear phenomena in models of the circadian clock

A scenario of unhealthy life cycle: The role of circadian rhythms in health

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