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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Updated: May 28, 2025

Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter
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ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins.

Hao-Yi Zhang1, Ke-Yun Li1, Yi-Li Wang1

  • 1College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China.

Redox Biology
|February 14, 2025
PubMed
Summary

Reactive oxygen species (ROS) disrupt circadian rhythms by altering EZH2 interactions with the CLOCK-BMAL1 complex. This finding reveals a key mechanism in oxidative stress-induced circadian disruption and aging.

Keywords:
Circadian rhythmOxidative stressROSZebrafishezh2

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Area of Science:

  • Molecular Biology
  • Chronobiology
  • Oxidative Stress Research

Background:

  • Accumulation of reactive oxygen species (ROS) and redox imbalance are linked to accelerated aging and diminished circadian rhythm amplitude.
  • The precise molecular mechanisms by which ROS impact circadian rhythms are not well understood.
  • Understanding these mechanisms is crucial for addressing age-related and circadian rhythm disorders.

Purpose of the Study:

  • To elucidate the role of reactive oxygen species (ROS) in disrupting circadian rhythms.
  • To identify key molecular players involved in ROS-mediated circadian disruption.
  • To investigate the interaction between oxidative stress, EZH2, and the core circadian clock machinery.

Main Methods:

  • Weighted gene co-expression network analysis (WGCNA) and machine learning (RF, LASSO, SVM) to identify key genes.
  • Utilized zebrafish and human cell models to study circadian rhythm disruption.
  • Employed genetic manipulation (ezh2 mutants, Morpholino, overexpression) and molecular assays (co-IP, ChIP, dual-luciferase reporter assays).

Main Results:

  • ROS were confirmed to disrupt circadian rhythms in zebrafish and human cells, affecting behavior and clock gene expression.
  • EZH2 was identified as a critical gene mediating the effects of ROS on circadian rhythms.
  • EZH2 was shown to interact with the CLOCK-BMAL1 complex, regulating clock gene transcription under oxidative stress.

Conclusions:

  • Reactive oxygen species disrupt circadian rhythms by modulating the interaction between EZH2 and the CLOCK-BMAL1 complex.
  • This study reveals a novel molecular pathway linking oxidative stress to circadian rhythm dysfunction.
  • Findings suggest EZH2 as a potential therapeutic target for age-related and circadian rhythm disorders.