Format

Send to

Choose Destination
PLoS Comput Biol. 2016 Dec 12;12(12):e1005266. doi: 10.1371/journal.pcbi.1005266. eCollection 2016 Dec.

Feedback Loops of the Mammalian Circadian Clock Constitute Repressilator.

Author information

1
Institute for Theoretical Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
2
Center for Functional Genomics and Biochips, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
3
Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Institute for Theoretical Biology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Abstract

Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as "repressilator" as a core element of the mammalian circadian oscillator. The central role of the repressilator motif is consistent with time-resolved ChIP-seq experiments of circadian clock transcription factors and loss of rhythmicity in core clock gene knockouts.

PMID:
27942033
PMCID:
PMC5189953
DOI:
10.1371/journal.pcbi.1005266
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center