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Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes
BACKGROUND: Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene ex...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332625/ https://www.ncbi.nlm.nih.gov/pubmed/30646953 http://dx.doi.org/10.1186/s13287-018-1118-4 |
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author | Davegårdh, Cajsa Hall Wedin, Elin Broholm, Christa Henriksen, Tora Ida Pedersen, Maria Pedersen, Bente Klarlund Scheele, Camilla Ling, Charlotte |
author_facet | Davegårdh, Cajsa Hall Wedin, Elin Broholm, Christa Henriksen, Tora Ida Pedersen, Maria Pedersen, Bente Klarlund Scheele, Camilla Ling, Charlotte |
author_sort | Davegårdh, Cajsa |
collection | PubMed |
description | BACKGROUND: Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene expression in primary human myoblasts (activated satellite cells) before and after differentiation into myotubes. METHOD: We used an array-based approach to analyse genome-wide DNA methylation and gene expression in myoblasts and myotubes from 13 women and 13 men. The results were followed up with a reporter gene assay. RESULTS: Genome-wide DNA methylation and gene expression differences between the sexes were detected in both myoblasts and myotubes, on the autosomes as well as the X-chromosome, despite lack of exposure to sex hormones and other factors that differ between sexes. Pathway analysis revealed higher expression of oxidative phosphorylation and other metabolic pathways in myoblasts from women compared to men. Oxidative phosphorylation was also enriched among genes with higher expression in myotubes from women. Forty genes in myoblasts and 9 in myotubes had differences in both DNA methylation and gene expression between the sexes, including LAMP2 and SIRT1 in myoblasts and KDM6A in myotubes. Furthermore, increased DNA methylation of LAMP2 promoter had negative effects on reporter gene expression. Five genes (CREB5, RPS4X, SYAP1, XIST, and ZRSR2) showed differential DNA methylation and gene expression between the sexes in both myoblasts and myotubes. Interestingly, differences in DNA methylation and expression between women and men were also found during differentiation (myoblasts versus myotubes), e.g., in genes involved in energy metabolism. Interestingly, more DNA methylation changes occur in women compared to men on autosomes. CONCLUSION: All together, we show that epigenetic and transcriptional differences exist in human myoblasts and myotubes as well as during differentiation between women and men. We believe that these intrinsic differences might contribute to sex dependent differences in muscular phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1118-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6332625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63326252019-01-16 Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes Davegårdh, Cajsa Hall Wedin, Elin Broholm, Christa Henriksen, Tora Ida Pedersen, Maria Pedersen, Bente Klarlund Scheele, Camilla Ling, Charlotte Stem Cell Res Ther Research BACKGROUND: Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene expression in primary human myoblasts (activated satellite cells) before and after differentiation into myotubes. METHOD: We used an array-based approach to analyse genome-wide DNA methylation and gene expression in myoblasts and myotubes from 13 women and 13 men. The results were followed up with a reporter gene assay. RESULTS: Genome-wide DNA methylation and gene expression differences between the sexes were detected in both myoblasts and myotubes, on the autosomes as well as the X-chromosome, despite lack of exposure to sex hormones and other factors that differ between sexes. Pathway analysis revealed higher expression of oxidative phosphorylation and other metabolic pathways in myoblasts from women compared to men. Oxidative phosphorylation was also enriched among genes with higher expression in myotubes from women. Forty genes in myoblasts and 9 in myotubes had differences in both DNA methylation and gene expression between the sexes, including LAMP2 and SIRT1 in myoblasts and KDM6A in myotubes. Furthermore, increased DNA methylation of LAMP2 promoter had negative effects on reporter gene expression. Five genes (CREB5, RPS4X, SYAP1, XIST, and ZRSR2) showed differential DNA methylation and gene expression between the sexes in both myoblasts and myotubes. Interestingly, differences in DNA methylation and expression between women and men were also found during differentiation (myoblasts versus myotubes), e.g., in genes involved in energy metabolism. Interestingly, more DNA methylation changes occur in women compared to men on autosomes. CONCLUSION: All together, we show that epigenetic and transcriptional differences exist in human myoblasts and myotubes as well as during differentiation between women and men. We believe that these intrinsic differences might contribute to sex dependent differences in muscular phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1118-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-15 /pmc/articles/PMC6332625/ /pubmed/30646953 http://dx.doi.org/10.1186/s13287-018-1118-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Davegårdh, Cajsa Hall Wedin, Elin Broholm, Christa Henriksen, Tora Ida Pedersen, Maria Pedersen, Bente Klarlund Scheele, Camilla Ling, Charlotte Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title_full | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title_fullStr | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title_full_unstemmed | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title_short | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
title_sort | sex influences dna methylation and gene expression in human skeletal muscle myoblasts and myotubes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332625/ https://www.ncbi.nlm.nih.gov/pubmed/30646953 http://dx.doi.org/10.1186/s13287-018-1118-4 |
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