EZH1 as a key mediator of exercise-induced H3K27me3 and H3K4me3 in mouse skeletal muscle
Epigenetic modification is a key mechanism that enhances the response of skeletal muscle to exercise training. Exercise-induced H3K27me3, which is co-modified with H3K4me3, is crucial for gene responses and adaptation in skeletal muscle; however, how exercise modifies H3K27me3 remains unclear. This...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2024-12-01
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| Series: | Advanced Exercise and Health Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950273X24000705 |
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| Summary: | Epigenetic modification is a key mechanism that enhances the response of skeletal muscle to exercise training. Exercise-induced H3K27me3, which is co-modified with H3K4me3, is crucial for gene responses and adaptation in skeletal muscle; however, how exercise modifies H3K27me3 remains unclear. This study aimed to test the hypothesis that exercise switches the H3K27me3 modifier from lysine methyltransferase enhancer of zest homolog 2 (EZH2) to EZH1. We first demonstrated that 4 weeks of running training significantly upregulated both H3K27me3 and H3K4me3 at the downstream regions of the transcription start site in exercise-related loci in the mouse tibialis anterior muscle. The distribution of suppressor of zeste 12, a component of polycomb repressive complex 2, also increased at these sites, while the distribution of EZH2 decreased after training. Next, we examined the effects of EZH1 overexpression on exercise training-induced H3K27me3 and H3K4me3. The combination of EZH1 overexpression and training led to a significantly greater increase in H3K4me3 compared to H3K27me3 at these loci, along with increased accumulation of related proteins, such as 70 kDa heat shock protein, muscle RING finger protein-1, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, and uncoupling protein 3, compared to exercise training alone. Furthermore, the expression of genes encoding these proteins in response to acute exercise was further enhanced by EZH1 overexpression, associated with the upregulation of both H3K27me3 and H3K4me3 at these loci. These findings suggest that exercise-induced H3K27me3 is primarily mediated by EZH1, which also plays a major role in modifying H3K4me3. |
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| ISSN: | 2950-273X |