DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice
Abstract Disuse muscle atrophy can result in downregulated gene expression vital to muscle integrity, yet the mechanisms driving this downregulation remain unclear. Epigenetic alterations regulate transcriptional potential, with repressive changes suppressing gene expression. This study explored epi...
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Wiley
2025-04-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70317 |
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| author | Junya Shimizu Fuminori Kawano |
| author_facet | Junya Shimizu Fuminori Kawano |
| author_sort | Junya Shimizu |
| collection | DOAJ |
| description | Abstract Disuse muscle atrophy can result in downregulated gene expression vital to muscle integrity, yet the mechanisms driving this downregulation remain unclear. Epigenetic alterations regulate transcriptional potential, with repressive changes suppressing gene expression. This study explored epigenetic mechanisms of gene downregulation during disuse muscle atrophy. Male C57BL/6J mice underwent hindlimb suspension for 3 or 7 days. The vastus intermedius (VI) muscle was analyzed, showing unchanged mass on day 3, but on day 7, decreased mass and reduced fiber size were assessed via immunohistochemistry. Corresponding to this atrophy timing, qPCR analysis revealed nine downregulated genes on day 7, which were selected for epigenetic analysis; collectively, they showed no downregulation on day 3. Among the nine genes, methylated DNA immunoprecipitation revealed significantly elevated DNA methylation (hypermethylation) in the upstream regions of transcription start sites (TSS) on day 7, which overall negatively correlated with gene expression. Histone marks (H3K27me3, H3K4me3, H3.3, and total H3) were also assessed using chromatin immunoprecipitation, revealing that the repressive histone mark H3K27me3 increased in the regions on day 3 but decreased on day 7. These findings suggest that DNA hypermethylation in the upstream regions preceded by H3K27me3 enrichment contributes to the downregulation of gene expression during disuse muscle atrophy. |
| format | Article |
| id | doaj-art-a450358398df4cd78effa124676887e0 |
| institution | OA Journals |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Physiological Reports |
| spelling | doaj-art-a450358398df4cd78effa124676887e02025-08-20T02:26:27ZengWileyPhysiological Reports2051-817X2025-04-01137n/an/a10.14814/phy2.70317DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male miceJunya Shimizu0Fuminori Kawano1Graduate School of Health Science Matsumoto University Nagano JapanGraduate School of Health Science Matsumoto University Nagano JapanAbstract Disuse muscle atrophy can result in downregulated gene expression vital to muscle integrity, yet the mechanisms driving this downregulation remain unclear. Epigenetic alterations regulate transcriptional potential, with repressive changes suppressing gene expression. This study explored epigenetic mechanisms of gene downregulation during disuse muscle atrophy. Male C57BL/6J mice underwent hindlimb suspension for 3 or 7 days. The vastus intermedius (VI) muscle was analyzed, showing unchanged mass on day 3, but on day 7, decreased mass and reduced fiber size were assessed via immunohistochemistry. Corresponding to this atrophy timing, qPCR analysis revealed nine downregulated genes on day 7, which were selected for epigenetic analysis; collectively, they showed no downregulation on day 3. Among the nine genes, methylated DNA immunoprecipitation revealed significantly elevated DNA methylation (hypermethylation) in the upstream regions of transcription start sites (TSS) on day 7, which overall negatively correlated with gene expression. Histone marks (H3K27me3, H3K4me3, H3.3, and total H3) were also assessed using chromatin immunoprecipitation, revealing that the repressive histone mark H3K27me3 increased in the regions on day 3 but decreased on day 7. These findings suggest that DNA hypermethylation in the upstream regions preceded by H3K27me3 enrichment contributes to the downregulation of gene expression during disuse muscle atrophy.https://doi.org/10.14814/phy2.70317disuse muscle atrophyDNA methylationepigenetic alterationsgene expressionH3K27me3 |
| spellingShingle | Junya Shimizu Fuminori Kawano DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice Physiological Reports disuse muscle atrophy DNA methylation epigenetic alterations gene expression H3K27me3 |
| title | DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| title_full | DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| title_fullStr | DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| title_full_unstemmed | DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| title_short | DNA hypermethylation preceded by H3K27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| title_sort | dna hypermethylation preceded by h3k27 trimethylation is linked to downregulation of gene expression in disuse muscle atrophy in male mice |
| topic | disuse muscle atrophy DNA methylation epigenetic alterations gene expression H3K27me3 |
| url | https://doi.org/10.14814/phy2.70317 |
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