Rethinking transcriptional activation in the Arabidopsis circadian clock

PLoS Comput Biol. 2014 Jul 17;10(7):e1003705. doi: 10.1371/journal.pcbi.1003705. eCollection 2014 Jul.

Abstract

Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis Proteins* / genetics
  • Arabidopsis Proteins* / metabolism
  • Arabidopsis* / genetics
  • Arabidopsis* / physiology
  • Circadian Clocks* / genetics
  • Circadian Clocks* / physiology
  • Computational Biology
  • Models, Genetic*
  • Transcription Factors
  • Transcriptional Activation* / genetics
  • Transcriptional Activation* / physiology

Substances

  • Arabidopsis Proteins
  • REVEILLE 8, protein Arabidopsis
  • Transcription Factors

Grant support

CT was supported by grant 2010-5219 from the Swedish Research Council, http://vr.se/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.