CIRCADIAN CLOCK-ASSOCIATED 1 regulates ROS homeostasis and oxidative stress responses

Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17129-34. doi: 10.1073/pnas.1209148109. Epub 2012 Oct 1.


Organisms have evolved endogenous biological clocks as internal timekeepers to coordinate metabolic processes with the external environment. Here, we seek to understand the mechanism of synchrony between the oscillator and products of metabolism known as Reactive Oxygen Species (ROS) in Arabidopsis thaliana. ROS-responsive genes exhibit a time-of-day-specific phase of expression under diurnal and circadian conditions, implying a role of the circadian clock in transcriptional regulation of these genes. Hydrogen peroxide production and scavenging also display time-of-day phases. Mutations in the core-clock regulator, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), affect the transcriptional regulation of ROS-responsive genes, ROS homeostasis, and tolerance to oxidative stress. Mis-expression of EARLY FLOWERING 3, LUX ARRHYTHMO, and TIMING OF CAB EXPRESSION 1 affect ROS production and transcription, indicating a global effect of the clock on the ROS network. We propose CCA1 as a master regulator of ROS homeostasis through association with the Evening Element in promoters of ROS genes in vivo to coordinate time-dependent responses to oxidative stress. We also find that ROS functions as an input signal that affects the transcriptional output of the clock, revealing an important link between ROS signaling and circadian output. Temporal coordination of ROS signaling by CCA1 and the reciprocal control of circadian output by ROS reveal a mechanistic link that allows plants to master oxidative stress responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / physiology*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • Arabidopsis Proteins / physiology*
  • Chromatin Immunoprecipitation
  • Computational Biology
  • Gene Expression Regulation, Plant / genetics
  • Gene Expression Regulation, Plant / physiology*
  • Homeostasis / genetics
  • Homeostasis / physiology*
  • Luminescent Measurements
  • Mutation / genetics
  • Oxidative Stress / physiology*
  • Polymerase Chain Reaction
  • Reactive Oxygen Species / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Arabidopsis Proteins
  • CCA1 protein, Arabidopsis
  • ELF3 protein, Arabidopsis
  • Lux Arrhythmo protein, Arabidopsis
  • Reactive Oxygen Species
  • TOC1 protein, Arabidopsis
  • Transcription Factors