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Androgen receptor function links human sexual dimorphism to DNA methylation

(2013) PLOS ONE. 8(9).
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Organization
Abstract
Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aberrant androgen receptor function is associated with distinct patterns of DNA-methylation marks in genital tissues. These findings support the concept that transcription factor binding to the DNA has an impact on the shape of the DNA methylome. These data which derived from a rare human model suggest that androgen programming of methylation marks contributes to sexual dimorphism in the human which might have considerable impact on the manifestation of sex-associated phenotypes and diseases.
Keywords
GENDER, EXPRESSION, GENE, HUMAN GENOME, HUMAN-DISEASE, PROGRAMMING WINDOW, X-INACTIVATION CENTER, PROSTATE-CANCER CELLS, PRENATAL TESTOSTERONE EXCESS, ENDOCRINE DISRUPTOR VINCLOZOLIN

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Chicago
Ammerpohl, Ole, Susanne Bens, Mahesh Appari, Ralf Werner, Bernhard Korn, Stenvert LS Drop, Frans Verheijen, et al. 2013. “Androgen Receptor Function Links Human Sexual Dimorphism to DNA Methylation.” Plos One 8 (9).
APA
Ammerpohl, O., Bens, S., Appari, M., Werner, R., Korn, B., Drop, S. L., Verheijen, F., et al. (2013). Androgen receptor function links human sexual dimorphism to DNA methylation. PLOS ONE, 8(9).
Vancouver
1.
Ammerpohl O, Bens S, Appari M, Werner R, Korn B, Drop SL, et al. Androgen receptor function links human sexual dimorphism to DNA methylation. PLOS ONE. 2013;8(9).
MLA
Ammerpohl, Ole, Susanne Bens, Mahesh Appari, et al. “Androgen Receptor Function Links Human Sexual Dimorphism to DNA Methylation.” PLOS ONE 8.9 (2013): n. pag. Print.
@article{4262439,
  abstract     = {Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aberrant androgen receptor function is associated with distinct patterns of DNA-methylation marks in genital tissues. These findings support the concept that transcription factor binding to the DNA has an impact on the shape of the DNA methylome. These data which derived from a rare human model suggest that androgen programming of methylation marks contributes to sexual dimorphism in the human which might have considerable impact on the manifestation of sex-associated phenotypes and diseases.},
  articleno    = {e73288},
  author       = {Ammerpohl, Ole and Bens, Susanne and Appari, Mahesh and Werner, Ralf and Korn, Bernhard and Drop, Stenvert LS and Verheijen, Frans and van der Zwan, Yvonne and Bunch, Trevor and Hughes, Leuan and Cools, Martine and Riepe, Felix G and Hiort, Olaf and Siebert, Reiner and Holterhus, Paul-Martin},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  language     = {eng},
  number       = {9},
  title        = {Androgen receptor function links human sexual dimorphism to DNA methylation},
  url          = {http://dx.doi.org/10.1371/journal.pone.0073288},
  volume       = {8},
  year         = {2013},
}

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