Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae
The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in <i>Drosophila</i> larvae carrying a temperature-sensitive mutation in the <i>shibire</i> (<i>shi<sup>1<...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/19/2333 |
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| author | Avivit Brener Dana Lorber Adriana Reuveny Hila Toledano Lilach Porat-Kuperstein Yael Lebenthal Eviatar Weizman Tsviya Olender Talila Volk |
| author_facet | Avivit Brener Dana Lorber Adriana Reuveny Hila Toledano Lilach Porat-Kuperstein Yael Lebenthal Eviatar Weizman Tsviya Olender Talila Volk |
| author_sort | Avivit Brener |
| collection | DOAJ |
| description | The biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in <i>Drosophila</i> larvae carrying a temperature-sensitive mutation in the <i>shibire</i> (<i>shi<sup>1</sup></i>) gene was induced to mimic sedentary behavior during early life and study its transcriptional outcome. Our findings indicated a significant change in the epigenetic profile, as well as the genomic profile, of RNA Pol II binding in the inactive muscles relative to control, within a relatively short time period. Whole-genome analysis of RNA-Pol II binding to DNA by muscle-specific targeted DamID (TaDa) protocol revealed that muscle inactivity altered Pol II binding in 121 out of 2010 genes (6%), with a three-fold enrichment of genes coding for lncRNAs. The suppressed protein-coding genes included genes associated with longevity, DNA repair, muscle function, and ubiquitin-dependent proteostasis. Moreover, inducing muscle inactivation exerted a multi-level impact upon chromatin modifications, triggering an altered epigenetic balance of active versus inactive marks. The downregulated genes in the inactive muscles included genes essential for muscle structure and function, carbohydrate metabolism, longevity, and others. Given the multiple analogous genes in <i>Drosophila</i> for many human genes, extrapolating our findings to humans may hold promise for establishing a molecular link between sedentary behavior and metabolic diseases. |
| first_indexed | 2024-03-10T21:47:24Z |
| format | Article |
| id | doaj.art-381ba57b9ce74b06adc644e383e79e0b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:47:24Z |
| publishDate | 2023-09-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-381ba57b9ce74b06adc644e383e79e0b2023-11-19T14:12:17ZengMDPI AGCells2073-44092023-09-011219233310.3390/cells12192333Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> LarvaeAvivit Brener0Dana Lorber1Adriana Reuveny2Hila Toledano3Lilach Porat-Kuperstein4Yael Lebenthal5Eviatar Weizman6Tsviya Olender7Talila Volk8Pediatric Endocrinology and Diabetes Institute, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelDepartment of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelPediatric Endocrinology and Diabetes Institute, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Affiliated with the Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelG-INCPM, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, IsraelThe biological mechanisms linking sedentary lifestyles and metabolic derangements are incompletely understood. In this study, temporal muscle inactivation in <i>Drosophila</i> larvae carrying a temperature-sensitive mutation in the <i>shibire</i> (<i>shi<sup>1</sup></i>) gene was induced to mimic sedentary behavior during early life and study its transcriptional outcome. Our findings indicated a significant change in the epigenetic profile, as well as the genomic profile, of RNA Pol II binding in the inactive muscles relative to control, within a relatively short time period. Whole-genome analysis of RNA-Pol II binding to DNA by muscle-specific targeted DamID (TaDa) protocol revealed that muscle inactivity altered Pol II binding in 121 out of 2010 genes (6%), with a three-fold enrichment of genes coding for lncRNAs. The suppressed protein-coding genes included genes associated with longevity, DNA repair, muscle function, and ubiquitin-dependent proteostasis. Moreover, inducing muscle inactivation exerted a multi-level impact upon chromatin modifications, triggering an altered epigenetic balance of active versus inactive marks. The downregulated genes in the inactive muscles included genes essential for muscle structure and function, carbohydrate metabolism, longevity, and others. Given the multiple analogous genes in <i>Drosophila</i> for many human genes, extrapolating our findings to humans may hold promise for establishing a molecular link between sedentary behavior and metabolic diseases.https://www.mdpi.com/2073-4409/12/19/2333agingepigeneticslncRNAproteostasissarcopeniaubiquitination |
| spellingShingle | Avivit Brener Dana Lorber Adriana Reuveny Hila Toledano Lilach Porat-Kuperstein Yael Lebenthal Eviatar Weizman Tsviya Olender Talila Volk Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae Cells aging epigenetics lncRNA proteostasis sarcopenia ubiquitination |
| title | Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae |
| title_full | Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae |
| title_fullStr | Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae |
| title_full_unstemmed | Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae |
| title_short | Sedentary Behavior Impacts on the Epigenome and Transcriptome: Lessons from Muscle Inactivation in <i>Drosophila</i> Larvae |
| title_sort | sedentary behavior impacts on the epigenome and transcriptome lessons from muscle inactivation in i drosophila i larvae |
| topic | aging epigenetics lncRNA proteostasis sarcopenia ubiquitination |
| url | https://www.mdpi.com/2073-4409/12/19/2333 |
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