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4 Publications visible to you, out of a total of 4
Testing the inferred transcription rates of a dynamic, gene network model in absolute units (in silico Plants 2021)

Abstract (Expand)

The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular … processes. However, models of the plant clock have largely been built and tested against RNA timeseries data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed model of the clock gene network in Arabidopsis thaliana. We re-interpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHY-CCA1-LIKE 5. The U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model KF2014, without greatly increasing model complexity. We tested the experimental error distributions of qRT-PCR data calibrated for units of RNA transcripts/cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previously-described circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptome-wide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts/cell/hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated clock models, FAIR data resources and a software environment in Docker, this validation process represents an advance in biochemical realism for models of plant gene regulation.

Authors: Uriel Urquiza Garcia, Andrew J Millar

Date Published: 5th Aug 2021

Publication Type: Journal

Testing the inferred transcription rates of a dynamic, gene network model in absolute units

Abstract (Expand)

The circadian clock coordinates plant physiology and development. Mathematical clock models have provided a rigorous framework to understand how the observed rhythms emerge from disparate, molecular … processes. However, models of the plant clock have largely been built and tested against RNA timeseries data in arbitrary, relative units. This limits model transferability, refinement from biochemical data and applications in synthetic biology. Here, we incorporate absolute mass units into a detailed, gene circuit model of the clock in Arabidopsis thaliana. We re-interpret the established P2011 model, highlighting a transcriptional activator that overlaps the function of REVEILLE 8/LHY-CCA1-LIKE 5, and refactor dynamic equations for the Evening Complex. The U2020 model incorporates the repressive regulation of PRR genes, a key feature of the most detailed clock model F2014, without greatly increasing model complexity. We tested the experimental error distributions of qRT-PCR data calibrated for units of RNA transcripts/cell and of circadian period estimates, in order to link the models to data more appropriately. U2019 and U2020 models were constrained using these data types, recreating previously-described circadian behaviours with RNA metabolic processes in absolute units. To test their inferred rates, we estimated a distribution of observed, transcriptome-wide transcription rates (Plant Empirical Transcription Rates, PETR) in units of transcripts/cell/hour. The PETR distribution and the equivalent degradation rates indicated that the models’ predicted rates are biologically plausible, with individual exceptions. In addition to updated, explanatory models of the plant clock, this validation process represents an advance in biochemical realism for models of plant gene regulation.

Authors: Uriel Urquiza-Garcia, Andrew J Millar

Date Published: 20th Mar 2021

Publication Type: Tech report

Rethinking Transcriptional Activation in the Arabidopsis Circadian Clock

Abstract

Not specified

Authors: Karl Fogelmark, Carl Troein

Date Published: 17th Jul 2014

Publication Type: Journal

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

Abstract (Expand)

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.

Authors: A. Pokhilko, A. P. Fernandez, K. D. Edwards, M. M. Southern, K. J. Halliday, A. J. Millar

Date Published: 6th Mar 2012

Publication Type: Not specified

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