Dataset Information

Locke2006_CircClock_LL

ABSTRACT: This a model from the article: Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana. Locke JC, Kozma-Bognár L, Gould PD, Fehér B, Kevei E, Nagy F, Turner MS, Hall A, Millar AJ Mol. Syst. Biol.2006;Volume:2;Page:59 17102804, Abstract: Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7), PRR9 and LHY and CCA1. This three-loop network explains the rhythmic phenotype of toc1 mutant alleles. Model predictions fit closely to new data on the gi;lhy;cca1 mutant, which confirm that GI is a major contributor to Y function. Analysis of the three-loop network suggests that the plant clock consists of morning and evening oscillators, coupled intracellularly, which may be analogous to coupled, morning and evening clock cells in Drosophila and the mouse. The model describes a three loops model of the Arabidopsis circadian clock. It provides initial conditions, parameter values and reactions for the production rates of the following species: LHY mRNA (cLm), cytoplasmic LHY (cLc), nuclear LHY (cLn), TOC1 mRNA (cTm), cytoplasmic TOC1 (cTc), nuclear TOC1 (cTn), X mRNA (cXm), cytoplasmic X (cXc), nuclear X (cXn), Y mRNA (cYm), cytoplasmic Y (cYc), nuclear Y (cYn), nuclear P (cPn), APRR7/9 mRNA, cytoplasmic APRR7/9, and nuclear APRR7/9. The paper describes the behaviour of the model in constant light (LL) and day-night cycle (LD). However, the current model only contains the LL cycle. Some parameter values should be changed from the wild-type (WT) ones in order to simulate the effect of mutations. These changes are listed in the notes of relevant parameters. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

SUBMITTER: Molecular Systems Biology

PROVIDER: BIOMD0000000089 | BioModels | 2007-02-20

REPOSITORIES: BioModels

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Publications

Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana.

Locke James C W JC Kozma-Bognár László L Gould Peter D PD Fehér Balázs B Kevei Eva E Nagy Ferenc F Turner Matthew S MS Hall Anthony A Millar Andrew J AJ

Molecular systems biology 20061114

Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7 ...[more]

PMID: 17102804

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Project description:Locke2005 - Circadian Clock SBML model of the interlocked feedback loop network The model describes the circuit depicted in Fig. 4 and reproduces the simulations in Figure 5A and 5B. It provides initial conditions, parameter values and rules for the production rates of the following species: LHY mRNA (cLm), cytoplasmic LHY (cLc), nuclear LHY (cLn), TOC1 mRNA (cTm), cytoplasmic TOC1 (cTc), nuclear TOC1 (cTn),X mRNA (cXm), cytoplasmic X (cXc), nuclear X (cXn), Y mRNA (cYm), cytoplasmic Y (cYc), nuclear Y (cYn), nuclear P (cPn). This model was successfully tested on MathSBML and SBML ODE Solver. Fig 5B is not in the right phase. However, the data is correct relative to the light/dark bars at the top of the figure. This model is described in the article: Extension of a genetic network model by iterative experimentation and mathematical analysis. Locke JC, Southern MM, Kozma-Bognár L, Hibberd V, Brown PE, Turner MS, Millar AJ Molecular Systems Biology [2005; 1: 2005.0013] 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. This model is hosted on BioModels Database and identified by: BIOMD0000000055 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:The first described feedback loop of the Arabidopsis circadian clock is based on reciprocal regulation between TOC1 and CCA1/LHY. CCA1 and LHY are MYB transcription factors that bind directly to the TOC1 promoter to negatively regulate its expression. Conversely, the activity of TOC1 has remained less well characterized. Genetic data supports that TOC1 is necessary for the reactivation of CCA1/LHY, but there is little description of its biochemical function. Here we show that TOC1 occupies specific genomic regions in the CCA1 and LHY promoters. Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA binding domains. Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1/LHY expression demonstrating that TOC1 can repress direct targets, and mutation or deletion of the CCT domain prevents this repression showing that DNA binding is necessary for TOC1 action. Furthermore, we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the Pseudoreceiver (PR) domain of the protein. To identify the genes regulated by TOC1 on a genomic scale, we couple TOC1 chemical induction with microarray analysis and identify new potential TOC1 targets and output pathways. Together these results define the biochemical action of the core clock protein TOC1 and refine our perspective on how plant clocks function. Keywords: Expression profiling by array wild type (Col-0) and ALC::TOC1 were sown on Murashige-Skoog with 0.8% agar, stratified for 48 hours and grown in12:12 light:dark (LD) for 12 days and either left in LD or transferred to constant light (LL) and then grown for one more day before the start of the experiment. Tissue was submerged in Murashige-Skoog media supplemented with 2.5% ethanol or no ethanol (mock) and with 20mM MG132 for 3 hours and harvested at ZT1. Three replicates each of the seedlings were collected and frozen in liquid nitrogen.

Dataset Information

Locke2006_CircClock_LL

Publications

Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana.

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