Epigenetics of Human Myometrium: DNA Methylation of Genes Encoding Contraction-Associated Proteins in Term and Preterm Labor.

Mitsuya K, Singh N, Sooranna SR, Johnson MR, Myatt L

Preterm birth involves the interaction of societal and environmental factors potentially modulating the length of gestation via the epigenome. An established form of epigenetic regulation is DNA methylation where promoter hypermethylation is associated with gene repression. We hypothesized we would find differences in DNA methylation in myometrium of women with preterm labor of different phenotypes vs. normal term labor. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor and twin gestations with labor. Genomic DNA was isolated, samples in each group combined and analyzed on a NimbleGen 2.1M human DNA methylation array. Differences in methylation from -8 to +3 kb of transcription start sites of 22 contraction-associated genes were determined. Cytosine methylation was not present in CpG islands of any gene but was present outside of CpG islands, in shores and shelves, in 19 genes. No differential methylation was found across the tissue groups for 6 genes (PTGES3, PTGER2, PTGER$, PTGFRN, ESR2 and GJA1). For 13 genes differential methylation occurred in several patterns between tissue groups. We find a correlation between hypomethylation and increased mRNA expression of PTGES, indicating potential functional relevance of methylation, but no such correlation for PTGS2 suggesting other regulatory mechanisms for PTGS2 at labor. The majority of differential DNA methylation of myometrial contraction-associated genes with different labor phenotypes occurs outside of CpG islands in gene promoters suggesting the entirety of DNA methylation across the genome should be considered.

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February, 2014



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