Open AccessExtension of a genetic network model by iterative experimentation and mathematical analysis
Author(s) -
Locke James C W,
Southern Megan M,
KozmaBognár László,
Hibberd Victoria,
Brown Paul E,
Turner Matthew S,
Millar Andrew J
Publication year - 2005
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb4100018
Subject(s) - biology , gigantea , circadian clock , arabidopsis thaliana , feedback loop , computational biology , arabidopsis , circadian rhythm , gene regulatory network , genetics , gene , biological system , gene expression , computer science , neuroscience , botany , mutant , computer security
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.