Androgen receptor function links human sexual dimorphism to DNA methylation.
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...
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2013
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oai:doaj.org-article:03b623fe9540465a8c8afa65e9ed53562021-11-18T08:56:56ZAndrogen receptor function links human sexual dimorphism to DNA methylation.1932-620310.1371/journal.pone.0073288https://doaj.org/article/03b623fe9540465a8c8afa65e9ed53562013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023855/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Sex 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.Ole AmmerpohlSusanne BensMahesh AppariRalf WernerBernhard KornStenvert L S DropFrans VerheijenYvonne van der ZwanTrevor BunchIeuan HughesMartine CoolsFelix G RiepeOlaf HiortReiner SiebertPaul-Martin HolterhusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73288 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Ole Ammerpohl Susanne Bens Mahesh Appari Ralf Werner Bernhard Korn Stenvert L S Drop Frans Verheijen Yvonne van der Zwan Trevor Bunch Ieuan Hughes Martine Cools Felix G Riepe Olaf Hiort Reiner Siebert Paul-Martin Holterhus Androgen receptor function links human sexual dimorphism to DNA methylation. |
| description |
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. |
| format |
article |
| author |
Ole Ammerpohl Susanne Bens Mahesh Appari Ralf Werner Bernhard Korn Stenvert L S Drop Frans Verheijen Yvonne van der Zwan Trevor Bunch Ieuan Hughes Martine Cools Felix G Riepe Olaf Hiort Reiner Siebert Paul-Martin Holterhus |
| author_facet |
Ole Ammerpohl Susanne Bens Mahesh Appari Ralf Werner Bernhard Korn Stenvert L S Drop Frans Verheijen Yvonne van der Zwan Trevor Bunch Ieuan Hughes Martine Cools Felix G Riepe Olaf Hiort Reiner Siebert Paul-Martin Holterhus |
| author_sort |
Ole Ammerpohl |
| title |
Androgen receptor function links human sexual dimorphism to DNA methylation. |
| title_short |
Androgen receptor function links human sexual dimorphism to DNA methylation. |
| title_full |
Androgen receptor function links human sexual dimorphism to DNA methylation. |
| title_fullStr |
Androgen receptor function links human sexual dimorphism to DNA methylation. |
| title_full_unstemmed |
Androgen receptor function links human sexual dimorphism to DNA methylation. |
| title_sort |
androgen receptor function links human sexual dimorphism to dna methylation. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/03b623fe9540465a8c8afa65e9ed5356 |
| work_keys_str_mv |
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