Enrichment of genes either hypo- or hypermethylated in AIS as compared to normal controls.

<p>The bar plots show percentage of loci either located in imprinted genes, genes containing either promoters with high CpG (HCP) or low CpG (LCP) content as well as the percentage of AR target genes as determined by the GATHER tool. Grey bars: percentage of genes present on the array, black bars: percentage of genes hypomethylated and white bars: percentage of genes hypermethylated in AIS patients. p-values have been determined applying χ²-test.</p

Array-based DNA methylation analysis of 26 AIS genital fibroblasts and 8 male control genital fibroblasts.

<p>(A) Supervised cluster analysis of DNA-methylation data obtained from genital fibroblasts separates individuals with AIS (yellow) from male controls (blue) (q<0.04). DNA-methylation is presented on a relative scale. To demonstrate reproducibility all hybridizations performed in duplicates are shown separately. (B) DNA-methylation of APOD (cg05624196) in fibroblasts lacking induction of APOD upon androgen treatment (non-responder) was significantly higher compared to responding fibroblasts (responder). (C) Variability in the DNA-methylation in AIS (yellow) compared to male controls (blue). Green: low, black: medium, red: high avg-beta values. The right bar indicates p-value (F-test).</p

Model of establishment of DNA methylation patterns by AR activity.

<p>(A) Unmutated inactive androgen receptor (AR) binds testosterone (T) activating the receptor. Activated AR binds directly (large arrow) to AR response elements on the DNA inducing gene expression which subsequently prevents DNA methylation (“gene1”). Additionally either the activated AR itself or AR induced genes act on suppressor complexes (S; dotted arrow) which repress particular sets of genes (“gene2”) leading finally to DNA methylation of silenced genes. (B) In AIS missing AR activity prevents activation of AR target genes which might subsequently result to (stochastic <i>de novo</i>) DNA methylation of affected genes. In contrast, genes usually silenced by AR (directly or by additional AR-dependent pathways) become expressed preventing DNA methylation. white lollipops: unmethylated DNA, filled lollipops: methylated DNA.</p