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The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops
Article first published online: 6 MAR 2012
Copyright © 2012 EMBO and Macmillan Publishers Limited
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Molecular Systems Biology
Volume 8, Issue 1, 2012
How to Cite
Pokhilko, A., Fernández, A. P., Edwards, K. D., Southern, M. M., Halliday, K. J. and Millar, A. J. (2012), The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops. Molecular Systems Biology, 8: n/a. doi: 10.1038/msb.2012.6
- Issue published online: 6 MAR 2012
- Article first published online: 6 MAR 2012
- Manuscript Accepted: 13 FEB 2012
- Manuscript Received: 9 AUG 2011
- biological clocks;
- circadian rhythms;
- gene regulatory networks;
- mathematical model;
- systems biology
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.
Recent findings are incorporated into a new mathematical model of the plant circadian clock, revealing a complex circuit structure comprised of multiple negative feedback loops, and predicting a repressive role for a key regulator, TOC1, which the authors confirm experimentally.
- The feedback structure of the plant clock's evening loop was reconstructed based on multiple data, and is now represented by the evening complex (ELF3-ELF4-LUX), which represses transcription from the ELF4 and LUX promoters.
- Computational analysis of timeseries data from mutant plants predicts that TOC1 is a repressor of the key morning genes LHY and CCA1, not an activator. Analysis of LHY and CCA1 expression in TOC1 gain- and loss-of-function plants confirms this prediction.
- Light induction of LHY and CCA1 expression is predicted to determine the clock's response to brief light pulses, matching the observed phase-response curve.
- The evening complex controls LHY and CCA1 expression by a double-negative connection, rather than direct activation, forming part of a three-component repressilator circuit, which is itself only part of the more complex circuit of the clock system.