ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000394 |
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| author | Hao-yi Zhang Ke-yun Li Yi-li Wang Chun-Jiao Wei Yu-Xuan Gao Ren-Zhou Ying-bin Zhong Zong-jun Yin Da-long Ren |
| author_facet | Hao-yi Zhang Ke-yun Li Yi-li Wang Chun-Jiao Wei Yu-Xuan Gao Ren-Zhou Ying-bin Zhong Zong-jun Yin Da-long Ren |
| author_sort | Hao-yi Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-65fbb72d72424af49094f4e2b003eae0 |
| institution | DOAJ |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-65fbb72d72424af49094f4e2b003eae02025-08-20T03:02:56ZengElsevierRedox Biology2213-23172025-04-018110352610.1016/j.redox.2025.103526ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteinsHao-yi Zhang0Ke-yun Li1Yi-li Wang2Chun-Jiao Wei3Yu-Xuan Gao4 Ren-Zhou5Ying-bin Zhong6Zong-jun Yin7Da-long Ren8College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaSchool of Biology & Basic Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu, 215000, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, ChinaCollege of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2213231725000394Oxidative stressROSCircadian rhythmezh2Zebrafish |
| spellingShingle | Hao-yi Zhang Ke-yun Li Yi-li Wang Chun-Jiao Wei Yu-Xuan Gao Ren-Zhou Ying-bin Zhong Zong-jun Yin Da-long Ren ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins Redox Biology Oxidative stress ROS Circadian rhythm ezh2 Zebrafish |
| title | ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins |
| title_full | ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins |
| title_fullStr | ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins |
| title_full_unstemmed | ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins |
| title_short | ROS regulates circadian rhythms by modulating Ezh2 interactions with clock proteins |
| title_sort | ros regulates circadian rhythms by modulating ezh2 interactions with clock proteins |
| topic | Oxidative stress ROS Circadian rhythm ezh2 Zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000394 |
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