Genome-Wide DNA Methylation Analysis Predicts an Epigenetic Switch for GATA Factor Expression in Endometriosis

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Women develop endometriosis when endometrial tissue with altered sensitivity to ovarian hormones grows outside the uterus. The persistent survival of these cells results in chronic pelvic pain and infertility. Although the origin of the disease remains a mystery, it only occurs in women and menstruating primates, suggesting that the unique evolution behind primate uterine development and menstruation are linked to the disease. Epigenetic defects affecting the uterine physiological response to ovarian hormones are also involved in endometriosis, and several genes implicated in disease progression are differentially methylated. Here we compared DNA methylation with gene expression in endometriosis using large-scale arrays. By comparing healthy and diseased cells treated with or without hormones to mimic part of the menstrual cycle, we uncovered many differentially methylated genes with defective expression in endometriosis that also regulate the hormone-dependent aspects of menstruation. In addition to expanding our understanding of how methylation affects endometriosis many fold, this also led us to propose an epigenetic switch that permits GATA6 expression in endometriosis instead of GATA2, and this switch promotes the aberrant expression of many of the genes seen in endometriosis. Our work provides novel unifying insight into the cause and development of endometriosis.

Vyšlo v časopise: Genome-Wide DNA Methylation Analysis Predicts an Epigenetic Switch for GATA Factor Expression in Endometriosis. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004158
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004158

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