Epigenetics of human myometrium: DNA methylation of genes encoding contraction-associated proteins in term and preterm labor

Kohzoh Mitsuya, Natasha Singh, Suren R. Sooranna, Mark R. Johnson, Leslie Myatt

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 the myometrium of women with preterm labor of different phenotypes versus 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, and samples in each group were 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 six genes (PTGES3L, PTGER2, PTGER4, 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/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, 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 that the entirety of DNA methylation across the genome should be considered.

Original languageEnglish (US)
Article number98
JournalBiology of Reproduction
Volume90
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Myometrium
Premature Obstetric Labor
DNA Methylation
Epigenomics
Methylation
CpG Islands
Genes
Proteins
Cyclooxygenase 2
Phenotype
Uterine Contraction
Pregnancy
Transcription Initiation Site
Cytosine
Premature Birth
Oligonucleotide Array Sequence Analysis
Cesarean Section
Genome
Messenger RNA
DNA

Keywords

  • Contraction
  • DNA methylation
  • Epigenetics
  • Epigenome
  • Methylome
  • Myometrium
  • Parturition
  • Pregnancy
  • Preterm labor

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Epigenetics of human myometrium : DNA methylation of genes encoding contraction-associated proteins in term and preterm labor. / Mitsuya, Kohzoh; Singh, Natasha; Sooranna, Suren R.; Johnson, Mark R.; Myatt, Leslie.

In: Biology of Reproduction, Vol. 90, No. 5, 98, 2014.

Research output: Contribution to journalArticle

@article{ab42becfd5144e8ab92e55913e128656,
title = "Epigenetics of human myometrium: DNA methylation of genes encoding contraction-associated proteins in term and preterm labor",
abstract = "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 the myometrium of women with preterm labor of different phenotypes versus 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, and samples in each group were 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 six genes (PTGES3L, PTGER2, PTGER4, 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/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, 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 that the entirety of DNA methylation across the genome should be considered.",
keywords = "Contraction, DNA methylation, Epigenetics, Epigenome, Methylome, Myometrium, Parturition, Pregnancy, Preterm labor",
author = "Kohzoh Mitsuya and Natasha Singh and Sooranna, {Suren R.} and Johnson, {Mark R.} and Leslie Myatt",
year = "2014",
doi = "10.1095/biolreprod.113.113209",
language = "English (US)",
volume = "90",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "5",

}

TY - JOUR

T1 - Epigenetics of human myometrium

T2 - DNA methylation of genes encoding contraction-associated proteins in term and preterm labor

AU - Mitsuya, Kohzoh

AU - Singh, Natasha

AU - Sooranna, Suren R.

AU - Johnson, Mark R.

AU - Myatt, Leslie

PY - 2014

Y1 - 2014

N2 - 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 the myometrium of women with preterm labor of different phenotypes versus 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, and samples in each group were 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 six genes (PTGES3L, PTGER2, PTGER4, 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/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, 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 that the entirety of DNA methylation across the genome should be considered.

AB - 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 the myometrium of women with preterm labor of different phenotypes versus 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, and samples in each group were 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 six genes (PTGES3L, PTGER2, PTGER4, 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/mPGES-1, indicating potential functional relevance of methylation, but no such correlation for PTGS2/COX-2, 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 that the entirety of DNA methylation across the genome should be considered.

KW - Contraction

KW - DNA methylation

KW - Epigenetics

KW - Epigenome

KW - Methylome

KW - Myometrium

KW - Parturition

KW - Pregnancy

KW - Preterm labor

UR - http://www.scopus.com/inward/record.url?scp=84903792473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903792473&partnerID=8YFLogxK

U2 - 10.1095/biolreprod.113.113209

DO - 10.1095/biolreprod.113.113209

M3 - Article

C2 - 24571989

AN - SCOPUS:84903792473

VL - 90

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 5

M1 - 98

ER -