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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...

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Autores principales: Davegårdh, Cajsa, Hall Wedin, Elin, Broholm, Christa, Henriksen, Tora Ida, Pedersen, Maria, Pedersen, Bente Klarlund, Scheele, Camilla, Ling, Charlotte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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.
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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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