Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator.

Authors
Carignano, Alberto 
Robertson, Fiona C 
Hearn, Timothy J 
Junyang, Jin 

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Abstract

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems.

Publication Date
2019-01
Online Publication Date
2019-01-31
Acceptance Date
2018-11-26
Keywords
Arabidopsis, Arabidopsis Proteins, Circadian Rhythm, Gene Expression Profiling, Gene Expression Regulation, Plant, Models, Biological, Niacinamide, Systems Biology, Transcriptome
Journal Title
PLoS Comput Biol
Journal ISSN
1553-734X
1553-7358
Volume Title
15
Publisher
Public Library of Science (PLoS)
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/I015558/1)
Biotechnology and Biological Sciences Research Council (BB/D017904/1)
Biotechnology and Biological Sciences Research Council (BB/L02182X/1)
Biotechnology and Biological Sciences Research Council (BB/S002251/1)
Engineering and Physical Sciences Research Council (EP/I03210X/1)
Biotechnology and Biological Sciences Research Council (BB/M00113X/1)
Biotechnology and Biological Sciences Research Council (BB/M006212/1)
Engineering and Physical Sciences Research Council (EP/E02761X/1)
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