Figure 8.

Genome-wide DNA methylation differences between stromal cells isolated from eutopic endometrium and endometriosis. The methylated (●) or unmethylated (○) state of a cytosine nucleotide in the CpG (or CG) sequence may in part regulate how genes are expressed in the DNA of a cell. (a) Schematic diagram of CpGs depicts their genomic context relative to the nearest CpG island (top) or gene (bottom). Gene contexts of CpGs were described as within an “island” (brown); on the “shore,” defined as within 4 kb around the island (yellow); or in “open sea,” defined as at least 4 kb distal from an island, and relative to the nearest open reading frame within 1500 bp (TSS1500; purple) or 200 bp (TSS200; pink) of a transcription start site (TSS); in the 5′ untranslated region (UTR), the first exon of a transcript (green); in the body of the gene (orange) or the 3′UTR (red). (b) Pie charts show the distribution of the CpGs examined based on their genomic context for all probes retained from the original array (top), for all the probes identified as differentially methylated between endometriosis and endometrium (middle), and for all the differentially methylated probes that were matched to differentially expressed mRNAs (bottom; note that stacked bar graphs show the CpG island context broken down for each of the gene contexts). A large number (5423) of differentially methylated CpG islands in this array were linked to a differentially expressed gene. A further integrative analysis demonstrated that 403 genes associated with one or more differentially methylated CpGs are differentially expressed with possible functional consequences. “Transcription factors” as a category comprised the most important gene category, whereas the top biologic pathway was “blood vessel development.” [Reproduced from Dyson MT, Roqueiro D, Monsivais D, et al. Genome-wide DNA methylation analysis predicts an epigenetic switch for GATA factor expression in endometriosis. PLoS Genet. 2014;10(3):e1004158. Copyright © 2014 by Dyson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.]