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Data assimilation constrains new connections and components in a complex, eukaryotic circadian clock model.

Pokhilko A, Hodge SK, Stratford K, Knox K, Edwards KD, Thomson AW, Mizuno T, Millar AJ - Mol. Syst. Biol. (2010)

Bottom Line: Our results suggest that the activation of important morning-expressed genes follows their release from a night inhibitor (NI).Experiments inspired by the new model support the predicted NI function and show that the PRR5 gene contributes to the NI.The multiple PRR genes of Arabidopsis uncouple events in the late night from light-driven responses in the day, increasing the flexibility of rhythmic regulation.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, UK.

ABSTRACT
Circadian clocks generate 24-h rhythms that are entrained by the day/night cycle. Clock circuits include several light inputs and interlocked feedback loops, with complex dynamics. Multiple biological components can contribute to each part of the circuit in higher organisms. Mechanistic models with morning, evening and central feedback loops have provided a heuristic framework for the clock in plants, but were based on transcriptional control. Here, we model observed, post-transcriptional and post-translational regulation and constrain many parameter values based on experimental data. The model's feedback circuit is revised and now includes PSEUDO-RESPONSE REGULATOR 7 (PRR7) and ZEITLUPE. The revised model matches data in varying environments and mutants, and gains robustness to parameter variation. Our results suggest that the activation of important morning-expressed genes follows their release from a night inhibitor (NI). Experiments inspired by the new model support the predicted NI function and show that the PRR5 gene contributes to the NI. The multiple PRR genes of Arabidopsis uncouple events in the late night from light-driven responses in the day, increasing the flexibility of rhythmic regulation.

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Related in: MedlinePlus

The main elements of the extended Arabidopsis circadian clock model. The previous circuit (Locke et al, 2006) is shown, upper right. Elements of the morning and evening oscillators are shown in yellow and grey, respectively. For clarity, proteins are shown only for ZTL, LHY modified (LHYmod) and TOC1 modified (TOC1mod). Genetic interactions, solid arrows; post-translational regulation, dashed arrows. Light inputs to gene transcription are marked by flashes. The full scheme of the model is presented in SBGN format in Supplementary Figure 1.
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f1: The main elements of the extended Arabidopsis circadian clock model. The previous circuit (Locke et al, 2006) is shown, upper right. Elements of the morning and evening oscillators are shown in yellow and grey, respectively. For clarity, proteins are shown only for ZTL, LHY modified (LHYmod) and TOC1 modified (TOC1mod). Genetic interactions, solid arrows; post-translational regulation, dashed arrows. Light inputs to gene transcription are marked by flashes. The full scheme of the model is presented in SBGN format in Supplementary Figure 1.

Mentions: Our previous model of Arabidopsis circadian clock (Locke et al, 2006) presented the core, three-loop structure of the clock, which comprised morning and evening oscillators and coupling between them (Figure 1). The morning loop included the dawn-expressed LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) genes, which negatively regulate their expression through activation of the inhibitor proteins, PSEUDO-RESPONSE REGULATOR 9 (PRR9) and PRR7. These were described by a single, combined model component, PRR9/7. The evening loop included the dusk-expressed gene TIMING OF CAB EXPRESSION 1 (TOC1), which negatively regulates itself through inhibition of a hypothetical activator, gene Y. The evening-expressed gene GIGANTEA (GI) contributes to Y function. The morning and evening loops were connected through inhibition of the evening genes by LHY/CCA1 and activation of LHY/CCA1 expression by a hypothetical evening gene X. Here, we extend the previous model of circadian gene expression (Locke et al, 2006) based on recently published data (Figure 1). The new model retains the good match of our previous model to the large volume of molecular time-series data, and improves the behaviour of the model clock system under a range of light conditions and in a wider range of mutants.


Data assimilation constrains new connections and components in a complex, eukaryotic circadian clock model.

Pokhilko A, Hodge SK, Stratford K, Knox K, Edwards KD, Thomson AW, Mizuno T, Millar AJ - Mol. Syst. Biol. (2010)

The main elements of the extended Arabidopsis circadian clock model. The previous circuit (Locke et al, 2006) is shown, upper right. Elements of the morning and evening oscillators are shown in yellow and grey, respectively. For clarity, proteins are shown only for ZTL, LHY modified (LHYmod) and TOC1 modified (TOC1mod). Genetic interactions, solid arrows; post-translational regulation, dashed arrows. Light inputs to gene transcription are marked by flashes. The full scheme of the model is presented in SBGN format in Supplementary Figure 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2964123&req=5

f1: The main elements of the extended Arabidopsis circadian clock model. The previous circuit (Locke et al, 2006) is shown, upper right. Elements of the morning and evening oscillators are shown in yellow and grey, respectively. For clarity, proteins are shown only for ZTL, LHY modified (LHYmod) and TOC1 modified (TOC1mod). Genetic interactions, solid arrows; post-translational regulation, dashed arrows. Light inputs to gene transcription are marked by flashes. The full scheme of the model is presented in SBGN format in Supplementary Figure 1.
Mentions: Our previous model of Arabidopsis circadian clock (Locke et al, 2006) presented the core, three-loop structure of the clock, which comprised morning and evening oscillators and coupling between them (Figure 1). The morning loop included the dawn-expressed LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) genes, which negatively regulate their expression through activation of the inhibitor proteins, PSEUDO-RESPONSE REGULATOR 9 (PRR9) and PRR7. These were described by a single, combined model component, PRR9/7. The evening loop included the dusk-expressed gene TIMING OF CAB EXPRESSION 1 (TOC1), which negatively regulates itself through inhibition of a hypothetical activator, gene Y. The evening-expressed gene GIGANTEA (GI) contributes to Y function. The morning and evening loops were connected through inhibition of the evening genes by LHY/CCA1 and activation of LHY/CCA1 expression by a hypothetical evening gene X. Here, we extend the previous model of circadian gene expression (Locke et al, 2006) based on recently published data (Figure 1). The new model retains the good match of our previous model to the large volume of molecular time-series data, and improves the behaviour of the model clock system under a range of light conditions and in a wider range of mutants.

Bottom Line: Our results suggest that the activation of important morning-expressed genes follows their release from a night inhibitor (NI).Experiments inspired by the new model support the predicted NI function and show that the PRR5 gene contributes to the NI.The multiple PRR genes of Arabidopsis uncouple events in the late night from light-driven responses in the day, increasing the flexibility of rhythmic regulation.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, UK.

ABSTRACT
Circadian clocks generate 24-h rhythms that are entrained by the day/night cycle. Clock circuits include several light inputs and interlocked feedback loops, with complex dynamics. Multiple biological components can contribute to each part of the circuit in higher organisms. Mechanistic models with morning, evening and central feedback loops have provided a heuristic framework for the clock in plants, but were based on transcriptional control. Here, we model observed, post-transcriptional and post-translational regulation and constrain many parameter values based on experimental data. The model's feedback circuit is revised and now includes PSEUDO-RESPONSE REGULATOR 7 (PRR7) and ZEITLUPE. The revised model matches data in varying environments and mutants, and gains robustness to parameter variation. Our results suggest that the activation of important morning-expressed genes follows their release from a night inhibitor (NI). Experiments inspired by the new model support the predicted NI function and show that the PRR5 gene contributes to the NI. The multiple PRR genes of Arabidopsis uncouple events in the late night from light-driven responses in the day, increasing the flexibility of rhythmic regulation.

Show MeSH
Related in: MedlinePlus