Dataset Information

Troein2011_ClockCircuit_OstreococcusTauri

ABSTRACT: This model is from the article: Multiple light inputs to a simple clock circuit allow complex biological rhythms Troein C, Corellou F, Dixon LE, van Ooijen G, O'Neill JS, Bouget FY, Millar AJ. Plant J.2011 Apr;66(2):375-85. 21219507, Abstract: Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable environmental changes. Detailed understanding of the circadian network of higher plants, such as Arabidopsis thaliana, is hampered by the high number of partially redundant genes. However, the picoeukaryotic alga Ostreococcus tauri, which was recently shown to possess a small number of non-redundant clock genes, presents an attractive alternative target for detailed modelling of circadian clocks in the green lineage. Based on extensive time-series data from in vivo reporter gene assays, we developed a model of the Ostreococcus clock as a feedback loop between the genes TOC1 and CCA1. The model reproduces the dynamics of the transcriptional and translational reporters over a range of photoperiods. Surprisingly, the model is also able to predict the transient behaviour of the clock when the light conditions are altered. Despite the apparent simplicity of the clock circuit, it displays considerable complexity in its response to changing light conditions. Systematic screening of the effects of altered day length revealed a complex relationship between phase and photoperiod, which is also captured by the model. The complex light response is shown to stem from circadian gating of light-dependent mechanisms. This study provides insights into the contributions of light inputs to the Ostreococcus clock. The model suggests that a high number of light-dependent reactions are important for flexible timing in a circadian clock with only one feedback loop. Note: Two-gene model of the Ostreococcus circadian clock This is a model of the circadian clock of Ostreococcus tauri, with a negative feedback loop between TOC1 and CCA1 (a.k.a. LHY) and multiple light inputs. It was used and described in Troein et al., Plant Journal (2011). The model incorporates luciferase reporters, and in this SBML model the four different versions of the model for transcriptional and translational reporter lines (pTOC1::LUC, pCCA1::LUC, TOC1-LUC and CCA1-LUC) are all accessible by setting one of the rep_X parameters to 1 and the others to 0. You can also set all four to 0 to only simulate the non-reporter core of the system. Input to the system should be provided by modifying the "light" function. An implementation of LD 12:12 is provided as an example, but the model was also used with more complicated light regimes that vary between data sets and are not convenient to express directly in SBML. The functions "ox_cca1" and "ox_toc1" can be altered to add overexpression of CCA1 and TOC1. Setting either to x gives additional, constitutive transcription at x times the maximal (and typically not realizable) transcription rate of the native gene. The overexpression mutant fits in Figure 7 of Troein et al. (2011) used ox_cca1 = 0.115 and oc_toc1 = 0.0584, respectively. The functions "copies_toc1" and "copies_cca1" are normally 1 but can be lowered to simulate knockdown experiments. The functions "transcription", "translation" and "proteasome" can be modified to simulate the effects of altering the overall rate of transcription, translation and protein degradation. The parameters were fitted specifically to data from transgenic reporter lines TOC8, pTOC3, LHY7 and pLHY7 (Corellou et al., Plant Cell 2009). Parameters that begin with "effcopies" describe the effective number of copies of CCA1 or TOC1 in the respective translational fusion lines, with anything above 1 due to the fusion proteins. For the model fitting, the initial values were fitted to the data in the various time courses. The initial values given here correspond to the limit cycle of the system in LD 12:12. The system converges to the limit cycle in just a few days under most light conditions, so these initial values are biologically meaningful. The species cca1luc_c and cca1luc_n have been merged into cca1luc (which corresponds to the observable luminescence signal), because Copasi refused to run the system otherwise. For TOC1-LUC, the predicted output signal is the sum of toc1luc_1 and toc1luc_2. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Andrew J Millar

PROVIDER: BIOMD0000000350 | BioModels | 2011-08-09

REPOSITORIES: BioModels

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Publications

Multiple light inputs to a simple clock circuit allow complex biological rhythms.

Troein Carl C Corellou Florence F Dixon Laura E LE van Ooijen Gerben G O'Neill John S JS Bouget François-Yves FY Millar Andrew J AJ

The Plant journal : for cell and molecular biology 20110401 2

Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable environmental changes. Detailed understanding of the circadian network of higher plants, such as Arabidopsis thaliana, is hampered by the high number of partially redundant genes. However, the picoeukaryotic alga Ostreococcus tauri, which was recently shown to possess a small number of non-redundant clock genes, presents an attractive alternative target for detailed modelling ...[more]

PMID: 21219507

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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.

Project description:The red-light regulated transcription factors FHY3 and FAR1 form a key point of light input to the plant circadian clock in positively regulating expression of genes within the central clock. However, the fhy3 mutant shows an additional red light-specific disruption of rhythmicity which is inconsistent with this role. Here we demonstrate that only fhy3 and not far1 mutants show this red specific disruption of rhythmicity. We examined the differences in rhythmic transcriptome in red versus white light and reveal differences in patterns of rhythmicity among the central clock proteins suggestive of a change in emphasis withing the central mechanism of the clock, changes which underlie the red specificity of the fhy3 mutant. In particular, changes in enrichment of promoter elements were consistent with a key role for the HY5 transcription factor, a known integrator of the ratio of red to blue light in regulation of the clock. Examination of differences in the rhythmic transcriptome in the fhy3 mutant in red light which identified specific disruption of the CCA1-regulated ELF3 and LUX central clock genes, while the CCA1 target TBS element, TGGGCC, was enriched among genes that became arrhythmic. Coupled with the known interaction of FHY3 but not FAR1 with CCA1 we propose that the red-specific circadian phenotype of fhy3 may involve disruption of the previously-demonstrated moderation of CCA1 activity by FHY3 rather than a disruption of its own transcriptional regulatory activity. Together, this evidence suggests a conditional redundancy between FHY3 and HY5 in the integration of red and blue light input to the clock in order to enable a plasticity in response to light and optimise plant adaptation. Furthermore, our evidence also suggests changes in CCA1 activity between red and white light transcriptomes. This, together with the documented interaction of HY5 with CCA1, leads us to propose a model whereby this integration of red and blue signals may at least partly occur via direct FHY3 and HY5 interaction with CCA1 leading to moderation of CCA1 activity.

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.

Dataset Information

Troein2011_ClockCircuit_OstreococcusTauri

Publications

Multiple light inputs to a simple clock circuit allow complex biological rhythms.

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