A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements

Jolley, Craig C, Ukai-Tadenuma, Maki, Perrin, Dimitri, & Ueda, Hiroki R (2014) A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements. Biophysical Journal, 107(6), pp. 1462-1473.

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Models of the mammalian clock have traditionally been based around two feedback loops-the self-repression of Per/Cry by interfering with activation by BMAL/CLOCK, and the repression of Bmal/Clock by the REV-ERB proteins. Recent experimental evidence suggests that the D-box, a transcription factor binding site associated with daytime expression, plays a larger role in clock function than has previously been understood. We present a simplified clock model that highlights the role of the D-box and illustrate an approach for finding maximum-entropy ensembles of model parameters, given experimentally imposed constraints. Parameter variability can be mitigated using prior probability distributions derived from genome-wide studies of cellular kinetics. Our model reproduces predictions concerning the dual regulation of Cry1 by the D-box and Rev-ErbA/ROR response element (RRE) promoter elements and allows for ensemble-based predictions of phase response curves (PRCs). Nonphotic signals such as Neuropeptide Y (NPY) may act by promoting Cry1 expression, whereas photic signals likely act by stimulating expression from the E/E' box. Ensemble generation with parameter probability restraints reveals more about a model's behavior than a single optimal parameter set.

Impact and interest:

3 citations in Scopus
2 citations in Web of Science®
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ID Code: 82686
Item Type: Journal Article
Refereed: Yes
DOI: 10.1016/j.bpj.2014.07.022
ISSN: 0006-3495
Divisions: Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Biophysical Society
Deposited On: 24 Mar 2015 02:50
Last Modified: 25 Jun 2017 18:33

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