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Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2, encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with 25 smoke exposure were less prominent than that of other genes. This suggests more conservative regulation on DNA methylation at these genes compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.... [Read More]
Total Size
2 files (83.1 MB)
Data Citation
Murphy, S. K., King, D. E., & Hoyo, C. (2022). Data from: Sex-specific dna methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes. Duke Research Data Repository. https://doi.org/10.7924/r44b36p48
Murphy, S. K., King, D. E., & Hoyo, C. (2022). Sex-specific dna methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes. Epigenetics, 17(12), 1573-1589. https://doi.org/10.1080/15592294.2022.2043591
Funding Agency
Environmental Protection Agency
National Institute of Diabetes and Digestive and Kidney Disease
National Institute of Environmental Health Sciences
