scholarly journals DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
D. C. Turner ◽  
P. P. Gorski ◽  
M. F. Maasar ◽  
R. A. Seaborne ◽  
P. Baumert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Activity ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Axon Guidance ◽  
Muscle Tissue ◽  
Focal Adhesion ◽  
Human Skeletal Muscle ◽  
Hox Genes ◽  
Skeletal Muscle Tissue

Abstract Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6–8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

scholarly journals DNA methylation across the genome in aged human skeletal muscle tissue and stem cells: The role of HOX genes and physical activity

2019 ◽  
Author(s):  
DC Turner ◽  
PP Gorski ◽  
MF Maasar ◽  
RA Seaborne ◽  
P Baumert ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Stem Cells ◽  
Axon Guidance ◽  
Muscle Tissue ◽  
Focal Adhesion ◽  
Human Skeletal Muscle ◽  
Hox Genes ◽  
Muscle Stem Cells

AbstractSkeletal muscle tissue demonstrates global hypermethylation with aging. However, methylome changes across the time-course of differentiation in aged human muscle derived stem cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged muscle stem cells over several time points of differentiation (0, 72 hours, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; ‘pathways-in-cancer’ (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), ‘rap1-signaling’, ‘axon-guidance’ and ‘hippo-signalling’. Aged muscle stem cells also demonstrated a hypermethylated profile in pathways; ‘axon-guidance’, ‘adherens-junction’ and ‘calcium-signaling’, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alteration in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in the ‘focal adhesion’ and ‘PI3K-AKT signalling’ pathways. While the methylomes were vastly different between muscle tissue and isolated muscle stem cells, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle and tissue and stem cells (on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P). Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and muscle stem cells and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue

2008 ◽  
Vol 131 (2) ◽  
pp. 181-189 ◽  
Author(s):  
A. Wiik ◽  
M. Ekman ◽  
O. Johansson ◽  
E. Jansson ◽  
M. Esbjörnsson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Oestrogen Receptor ◽  
Human Skeletal Muscle ◽  
Skeletal Muscle Tissue ◽  
Receptor Alpha ◽  
Oestrogen Receptor Alpha

The response of human skeletal muscle tissue to hypoxia

2009 ◽  
Vol 66 (22) ◽  
pp. 3615-3623 ◽  
Author(s):  
Carsten Lundby ◽  
Jose A. L. Calbet ◽  
Paul Robach
Keyword(s):  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Human Skeletal Muscle ◽  
Skeletal Muscle Tissue

scholarly journals Integrative methylome and transcriptome analysis of Japanese flounder (Paralichthys olivaceus) skeletal muscle during development

2019 ◽  
Author(s):  
Jingru Zhang ◽  
Shuxian Wu ◽  
Yajuan Huang ◽  
Haishen Wen ◽  
Meizhao Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Axon Guidance ◽  
Muscle Tissue ◽  
Muscle Development ◽  
Adherens Junction ◽  
Japanese Flounder ◽  
Gene Body ◽  
Skeletal Muscle Development ◽  
Genome Wide

AbstractDNA methylation is an important epigenetic modification in vertebrate and is essential for epigenetic gene regulation in skeletal muscle development. We showed the genome-wide DNA methylation profile in skeletal muscle tissue of larval 7dph (JP1), juvenile 90dph (JP2), adult female 24 months (JP3) and adult male 24 months (JP4) Japanese flounder. The distribution and levels of methylated DNA within genomic features (1stexons, gene body, introns, TSS200, TSS1500 and intergenic) show different developmental landscapes. We also successfully identified differentially methylated regions (DMRs) and different methylated genes (DMGs) through a comparative analysis, indicating that DMR in gene body, intron and intergenic regions were more compared to other regions of all DNA elements. A gene ontology analysis indicated that the DMGs were mainly related to regulation of skeletal muscle fiber development process, Axon guidance, Adherens junction, and some ATPase activity. Methylome and transcriptome clearly revealed a exhibit a negative correlation. And integration analysis revealed a total of 425, 398 and 429 negatively correlated genes with methylation in the JP2_VS_JP1, JP3_VS_JP1 and JP4_VS_JP1 comparison groups, respectively. And these genes were functionally associated with pathways including Adherens junction, Axon guidance, Focal adhesion, cell junctions, Actin cytoskeleton and Wnt signaling pathways. In addition, we validated the MethylRAD results by bisulfite sequencing PCR (BSP) in some of the differentially methylated skeletal muscle growth-related genes (Myod1, Six1 and Ctnnb1). In this study, we have generated the genome-wide profile of methylome and transcriptome in Japanese flounder for the first time, and our results bring new insights into the epigenetic regulation of developmental processes in Japanese flounder. This study contributes to the knowledge on epigenetics in vertebrates.Author summaryEpigenetic mechanisms like DNA methylation have recently reported as vital regulators of some species skeletal muscle development through the control of genes related to growth. To date, although genome-wide DNA methylation profiles of many organisms have been reported and the Japanese flounder reference genome and whole transcriptome data are publically available, the methylation pattern of Japanese flounder skeletal muscle tissue remains minimally studied and the global DNA methylation data are yet to be known. Here we investigated the genome-wide DNA methylation patterns in Japanese flounder, throughout its development. These findings help to enrich research in molecular and developmental biology in vertebrates.

scholarly journals Differential Gene Expression in Cell Types of the Human Skeletal Muscle: A Bioinformatics-Based Meta-Review

2021 ◽  
Vol 30 (4) ◽  
pp. 444-452
Author(s):  
Kyung-Wan Baek ◽  
So-Jeong Kim ◽  
Ji-Seok Kim ◽  
Sun-Ok Kwon
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Tissue ◽  
Cultured Cells ◽  
Cell Types ◽  
Gene Expression Omnibus ◽  
Skeletal Muscle Tissue ◽  
Exercise Science ◽  
Ncbi Gene Expression Omnibus ◽  
Genes Encoding

PURPOSE: This study evaluates the differences in the expression of genes frequently analyzed in the field of exercise science between the skeletal muscle tissue and various cell types that comprise the skeletal muscle tissue.METHODS: We summarized the genes and proteins expressed in the skeletal muscle that were published in “Exercise Science” journal from 2015 to present. Thereafter, we selected 15 genes and proteins that were the most analyzed genes and proteins in the skeletal muscle. These genes and proteins were horizontally compared for expression differences in skeletal muscle components and cultured cells based on NCBI Gene Expression Omnibus DataSets.RESULTS: The most analyzed genes (encoding analyzed proteins) in skeletal muscle tissues in “Exercise Science” were PPARGC1A, PPARD, MTOR, MAP1LC3A, MAP1LC3B, PRKAA1, AKT1, SLC2A4, MAPK1, COX4I1, MAPK14, MEF2A, MAPK8, RPS6KB1, and SOD1. Among them, PPARGC1A, AKT1, SLC2A4, MAPK1, and COX4I1 were specifically expressed in the skeletal muscle. However, expression of other genes was found to be significantly affected in other cell types of the skeletal muscle tissue.CONCLUSIONS: Genes such as PPARGC1A, which are specifically expressed in the skeletal muscle, may be analyzed without pretreating (such as perfusion) the skeletal muscle tissue. However, expression of other genes may depend on the skeletal muscle cell type. Thus, in such instances, pretreatment, such as perfusion and isolation, should be considered.

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