PUBLICATION
ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins
- Authors
- Zhang, H.Y., Li, K.Y., Wang, Y.L., Wei, C.J., Gao, Y.X., Ren-Zhou, ., Zhong, Y.B., Yin, Z.J., Ren, D.L.
- ID
- ZDB-PUB-250216-3
- Date
- 2025
- Source
- Redox Biology 81: 103526103526 (Journal)
- Registered Authors
- Zhong, Yingbin
- Keywords
- Circadian rhythm, Oxidative stress, ROS, Zebrafish, ezh2
- MeSH Terms
-
- Animals
- Oxidative Stress
- ARNTL Transcription Factors/genetics
- ARNTL Transcription Factors/metabolism
- Circadian Rhythm*/genetics
- Zebrafish*/genetics
- Humans
- Reactive Oxygen Species*/metabolism
- CLOCK Proteins*/genetics
- CLOCK Proteins*/metabolism
- Enhancer of Zeste Homolog 2 Protein*/genetics
- Enhancer of Zeste Homolog 2 Protein*/metabolism
- Gene Expression Regulation
- Protein Binding
- PubMed
- 39952198 Full text @ Redox Biol.
Citation
Zhang, H.Y., Li, K.Y., Wang, Y.L., Wei, C.J., Gao, Y.X., Ren-Zhou, ., Zhong, Y.B., Yin, Z.J., Ren, D.L. (2025) ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins. Redox Biology. 81:103526103526.
Abstract
Redox imbalance induced by the accumulation of reactive oxygen species (ROS) accelerates age-related processes, often accompanied by a decrease in circadian rhythm amplitude. However, the underlying mechanisms by which ROS modulate circadian rhythms remain poorly understood. In this study, we found that ROS disrupt circadian rhythms in both zebrafish, as indicated by changes in diurnal behavior and clock gene expression, and in a human cell model. Using weighted gene co-expression network analysis (WGCNA) and machine learning approaches (RF, LASSO, SVM), EZH2 was identified as a key gene involved in regulating circadian rhythms under oxidative stress conditions. To further investigate the role of EZH2, we employed ezh2-/- mutants, Morpholino injection, and overexpression treatment and discovered that EZH2 is crucial in mediating the effect of ROS on circadian rhythms. Furthermore, EZH2 interacts with the CLOCK-BMAL1 complex to regulate the transcription of clock genes, as demonstrated through co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. Our study revealed that ROS disrupt circadian rhythms by regulating the interaction between EZH2 and the CLOCK-BMAL1 complex, shedding light on the molecular mechanisms of circadian rhythm disruption under oxidative stress and suggesting potential targets for age-related and circadian disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping