The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops

Alexandra Pokhilko, Aurora Pinas Fernandez, Kieron D. Edwards, Megan M. Southern, Karen J. Halliday, Andrew J. Millar

Research output: Contribution to journalArticlepeer-review

325 Citations (Scopus)


Circadian clocks synchronise biological processes with the day/night cycle, using molecular mechanisms that include interlocked, transcriptional feedback loops. Recent experiments identified the evening complex (EC) as a repressor that can be essential for gene expression rhythms in plants. Integrating the EC components in this role significantly alters our mechanistic, mathematical model of the clock gene circuit. Negative autoregulation of the EC genes constitutes the clock's evening loop, replacing the hypothetical component Y. The EC explains our earlier conjecture that the morning gene PSEUDO-RESPONSE REGULATOR 9 was repressed by an evening gene, previously identified with TIMING OF CAB EXPRESSION1 (TOC1). Our computational analysis suggests that TOC1 is a repressor of the morning genes LATE ELONGATED HYPOCOTYL and CIRCADIAN CLOCK ASSOCIATED1 rather than an activator as first conceived. This removes the necessity for the unknown component X (or TOC1mod) from previous clock models. As well as matching timeseries and phase-response data, the model provides a new conceptual framework for the plant clock that includes a three-component repressilator circuit in its complex structure. Molecular Systems Biology 8: 574; published online 6 March 2012; doi:10.1038/msb.2012.6 Subject Categories: metabolic and regulatory networks; plant biology

Original languageEnglish
Article number574
Number of pages13
JournalMolecular Systems Biology
Publication statusPublished - Mar 2012


  • biological clocks
  • circadian rhythms
  • gene regulatory networks
  • mathematical model
  • systems biology
  • pseudo-response regulators
  • box protein zeitlupe
  • circadian clock
  • flowering time
  • ubiquitin ligase
  • blue-light
  • rhythms
  • TOC1
  • thaliana
  • gigantea


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