Modelling the widespread effects of TOC1 signalling on the plant circadian clock and its outputs
1 School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JH, UK
2 Centre for Research in Agricultural Genomics (CRAG), Consortium CSIC-IRTA-UAB-UB, Parc de Recerca UAB, Bellaterra (Cerdanyola del Vallés), 08193, BarcelonaSpain
3 SynthSys, University of Edinburgh, C.H. Waddington Building, Mayfield Road, Edinburgh, EH9 3JD, UK
4 Institute for Complex Systems and Mathematical Biology, University of Aberdeen, Meston Building, Aberdeen, AB24 3UE, UK
BMC Systems Biology 2013, 7:23 doi:10.1186/1752-0509-7-23Published: 19 March 2013
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.
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.
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.