title: Extension of a genetic network model by iterative experimentation and mathematical analysis.
abstract: Circadian clocks involve feedback loops that generate rhythmic expression of key genes. Molecular genetic studies in the higher plant Arabidopsis thaliana have revealed a complex clock network. The first part of the network to be identified, a transcriptional feedback loop comprising TIMING OF CAB EXPRESSION 1 (TOC1), LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), fails to account for significant experimental data. We develop an extended model that is based upon a wider range of data and accurately predicts additional experimental results. The model comprises interlocking feedback loops comparable to those identified experimentally in other circadian systems. We propose that each loop receives input signals from light, and that each loop includes a hypothetical component that had not been explicitly identified. Analysis of the model predicted the properties of these components, including an acute light induction at dawn that is rapidly repressed by LHY and CCA1. We found this unexpected regulation in RNA levels of the evening-expressed gene GIGANTEA (GI), supporting our proposed network and making GI a strong candidate for this component.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry, UK.
authors.forename: James C W
authors.initials: JC
authors.lastname: Locke
authors.forename: Megan M
authors.initials: MM
authors.lastname: Southern
authors.forename: László
authors.initials: L
authors.lastname: Kozma-Bognár
authors.forename: Victoria
authors.initials: V
authors.lastname: Hibberd
authors.forename: Paul E
authors.initials: PE
authors.lastname: Brown
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Turner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Millar
mesh_terms: D017360:Arabidopsis / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D029681:Arabidopsis Proteins / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological; D018506:Gene Expression Regulation, Plant / Q000528:radiation effects; D008027:Light; D008957:Models, Genetic; D015398:Signal Transduction / Q000528:radiation effects; D049490:Systems Biology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D029681:Arabidopsis Proteins; C114425:CCA1 protein, Arabidopsis; D004268:DNA-Binding Proteins; C121183:GI protein, Arabidopsis; C113192:LHY protein, Arabidopsis; C411822:TOC1 protein, Arabidopsis; D014157:Transcription Factors