Diagenode

Genome-wide DNA methylation and transcriptome integration reveal distinct sex differences in skeletal muscle


Shanie Landen, Macsue Jacques , Danielle Hiam , Javier Alvarez, Nicholas R Harvey, Larisa M. Haupt, Lyn R, Griffiths, Kevin J Ashton, Séverine Lamon, Sarah Voisin, Nir Eynon

Nearly all human complex traits and diseases exhibit some degree of sex differences, and epigenetics contributes to these differences as DNA methylation shows sex differences in various tissues. However, skeletal muscle epigenetic sex differences remain largely unexplored, yet skeletal muscle displays distinct sex differences at the transcriptome level. We conducted a large-scale meta-analysis of autosomal DNA methylation sex differences in human skeletal muscle in three separate cohorts (Gene SMART, FUSION, and GSE38291), totalling n = 369 human muscle samples (n = 222 males, n = 147 females). We found 10,240 differentially methylated regions (DMRs) at FDR < 0.005, 94% of which were hypomethylated in males, and gene set enrichment analysis revealed that differentially methylated genes were involved in muscle contraction and metabolism. We then integrated our epigenetic results with transcriptomic data from the GTEx database and the FUSION cohort. Altogether, we identified 326 autosomal genes that display sex differences at both the DNA methylation, and transcriptome levels. Importantly, sex-biased genes at the transcriptional level were overrepresented among the sex-biased genes at the epigenetic level (p-value = 4.6e-13), which suggests differential DNA methylation and gene expression between males and females in muscle are functionally linked. Finally, we validated expression of three genes with large effect sizes (FOXO3A, ALDH1A1, and GGT7) in the Gene SMART cohort with qPCR. GGT7, involved in muscle metabolism, displays male-biased expression in skeletal muscle across the three cohorts, as well as lower methylation in males. In conclusion, we uncovered thousands of genes that exhibit DNA methylation differences between the males and females in human skeletal muscle that may modulate mechanisms controlling muscle metabolism and health.

Tags
DNA methylation microarray
Muscle metabolism
Epigenetic sex difference

Share this article

Published
March, 2021

Source

Products used in this publication

  • default alt
    G02090000
    Illumina Infinium MethylationEPIC array BeadChi...

活动

  • Virtual ChIL-seq webinar
    Diagenode
    Dec 8, 2021
 查看所有活动

新闻

 查看所有新闻


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics