Dataset Information

Pokhilko2012_CircClock_RepressilatorFeedbackloop

ABSTRACT: This model is from the article: The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops Pokhilko A, Fernández AP, Edwards KD, Southern MM, Halliday KJ, Millar AJ. Mol Syst Biol.2012 Mar 6;8:574. 22395476, Abstract: 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.

OTHER RELATED OMICS DATASETS IN: PRJNA120931

SUBMITTER: Alexandra Pokhilko

PROVIDER: BIOMD0000000412 | BioModels | 2011-08-18

REPOSITORIES: BioModels

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Publications

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

Pokhilko Alexandra A Fernández Aurora Piñas AP Edwards Kieron D KD Southern Megan M MM Halliday Karen J KJ Millar Andrew J AJ

Molecular systems biology 20120306

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, rep ...[more]

PMID: 22395476

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Project description:Pokhilko2013 - TOC1 signalling in Arabidopsis circadian clock In this model, Pokhilko et al. has incorporated the negative transcriptional regulations of the core clock genes by TOC1 and the up-regulation of TOC1 expression by ABA signalling, to their previous model BIOMD0000000412 This model is described in the article: Modelling the widespread effects of TOC1 signalling on the plant circadian clock and its outputs. Pokhilko A, Mas P, Millar AJ. BMC Syst Biol 2013; 7: 23 Abstract: BACKGROUND: 24-hour biological clocks are intimately connected to the cellular signalling network, which complicates the analysis of clock mechanisms. The transcriptional regulator TOC1 (TIMING OF CAB EXPRESSION 1) is a founding component of the gene circuit in the plant circadian clock. Recent results show that TOC1 suppresses transcription of multiple target genes within the clock circuit, far beyond its previously-described regulation of the morning transcription factors LHY (LATE ELONGATED HYPOCOTYL) and CCA1 (CIRCADIAN CLOCK ASSOCIATED 1). It is unclear how this pervasive effect of TOC1 affects the dynamics of the clock and its outputs. TOC1 also appears to function in a nested feedback loop that includes signalling by the plant hormone Abscisic Acid (ABA), which is upregulated by abiotic stresses, such as drought. ABA treatments both alter TOC1 levels and affect the clock's timing behaviour. Conversely, the clock rhythmically modulates physiological processes induced by ABA, such as the closing of stomata in the leaf epidermis. In order to understand the dynamics of the clock and its outputs under changing environmental conditions, the reciprocal interactions between the clock and other signalling pathways must be integrated. RESULTS: We extended the mathematical model of the plant clock gene circuit by incorporating the repression of multiple clock genes by TOC1, observed experimentally. The revised model more accurately matches the data on the clock's molecular profiles and timing behaviour, explaining the clock's responses in TOC1 over-expression and toc1 mutant plants. A simplified representation of ABA signalling allowed us to investigate the interactions of ABA and circadian pathways. Increased ABA levels lengthen the free-running period of the clock, consistent with the experimental data. Adding stomatal closure to the model, as a key ABA- and clock-regulated downstream process allowed to describe TOC1 effects on the rhythmic gating of stomatal closure. CONCLUSIONS: The integrated model of the circadian clock circuit and ABA-regulated environmental sensing allowed us to explain multiple experimental observations on the timing and stomatal responses to genetic and environmental perturbations. These results crystallise a new role of TOC1 as an environmental sensor, which both affects the pace of the central oscillator and modulates the kinetics of downstream processes. This model is hosted on BioModels Database and identified by: BIOMD0000000445. 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: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.

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.

Dataset Information

Pokhilko2012_CircClock_RepressilatorFeedbackloop

Publications

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

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