Related Experiment Video
Updated: May 25, 2026
09:32
Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
CHD4 is a copper sensor linking chromatin remodeling to cuproptosis
Yongjie Wang1, Runqiu Chi2, Congcong Zhang2
1Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; Shanghai Key Laboratory of Thoracic Tumor Biotherapy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China; Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Free Radical Biology & Medicine
|May 23, 2026
Summary
Cuproptosis, a copper-regulated cell death, is linked to epigenetics. Researchers found the protein CHD4 senses copper, controlling cell death via the HSF2-FDX1 pathway, offering new therapeutic targets.
Area of Science:
- Cell Biology
- Epigenetics
- Molecular Oncology
Background:
- Cuproptosis is a copper-dependent regulated cell death (RCD) pathway.
- The link between cuproptosis and epigenetic regulation, particularly chromatin, remains largely unexplored.
Purpose of the Study:
- To elucidate the connection between chromatin regulation and cuproptosis sensitivity.
- To identify molecular players mediating copper sensing in cell death pathways.
Main Methods:
- Multi-omics analyses (including chromatin accessibility and histone modifications).
- Biochemical assays to study protein-copper interactions.
- Genetic manipulation and pharmacological treatments in cell and patient-derived models.
Main Results:
- Cuproptosis-sensitive cells display an epigenetically primed state with increased chromatin accessibility.
- The chromatin remodeler CHD4 acts as a direct copper sensor, undergoing degradation upon copper binding.
- Loss of CHD4 leads to HSF2 de-repression, which activates FDX1, a key cuproptosis executor, establishing the copper-CHD4-HSF2-FDX1 axis.
- High HSF2/FDX1 expression correlates with enhanced response to cuproptosis inducers in patient models.
Conclusions:
- An epigenetic mechanism links copper sensing to cuproptosis.
- The CHD4/HSF2/FDX1 axis is a critical regulator of cuproptosis susceptibility.
- This axis represents potential biomarkers and therapeutic targets for precision oncology.
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