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Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: Prediction of RevErb-α up-regulation during mitosis
Abstract : Experimental observations have put in evidence autonomous self-sustained circadian oscillators in most mammalian cells, and proved the existence of molecular links between the circadian clock and the cell cycle. Some mathematical models have also been built to assess conditions of control of the cell cycle by the circadian clock. However, recent studies in individual NIH3T3 fibroblasts have shown an unexpected acceleration of the circadian clock together with the cell cycle when the culture medium is enriched with growth factors, and the absence of such acceleration in confluent cells. In order to explain these observations , we study a possible entrainment of the circadian clock by the cell cycle through a regulation of clock genes around the mitosis phase. We develop a computational model and a formal specification of the observed behavior to investigate the conditions of entrainment in period and phase. We show that either the selective activation of RevErb-α or the selective inhibition of Bmal1 transcription during the mitosis phase, allow us to fit the experimental data on both period and phase, while a uniform inhibition of transcription during mitosis seems incompatible with the phase data. We conclude on the arguments favouring the RevErb-α up-regulation hypothesis and on some further predictions of the model.
Cited literature [33 references]
https://hal.archives-ouvertes.fr/hal-01378466
Contributor : Sylvain Soliman <>
Submitted on : Thursday, November 10, 2016 - 4:43:36 PM
Last modification on : Monday, June 14, 2021 - 10:24:51 AM
Long-term archiving on: : Monday, March 20, 2017 - 5:06:32 PM
Contributor : Sylvain Soliman <>
Submitted on : Thursday, November 10, 2016 - 4:43:36 PM
Last modification on : Monday, June 14, 2021 - 10:24:51 AM
Long-term archiving on: : Monday, March 20, 2017 - 5:06:32 PM
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TFS16biosystems.pdf
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