Cytosine methylation dysregulation in neonates following intrauterine growth restriction

Francine Einstein, Reid F. Thompson, Tushar D. Bhagat, Melissa J. Fazzari, Amit K. Verma, Nir Barzilai, John M. Greally

Research output: Contribution to journalArticle

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Abstract

Background: Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings: Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions: Our results give insights into the potential contribution of epigenomic dysregulation in mediating the longterm consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

Original languageEnglish (US)
Article numbere8887
JournalPLoS One
Volume5
Issue number1
DOIs
StatePublished - Jan 26 2010

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Methylation
cytosine
Cytosine
methylation
neonates
loci
Genes
DNA methylation
DNA Methylation
Medical problems
Growth
Hematopoietic Stem Cells
Epigenomics
epigenetics
Hepatocyte Nuclear Factor 4
fetal development
Fetal Development
Stem cells
Fetal Blood
noninsulin-dependent diabetes mellitus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cytosine methylation dysregulation in neonates following intrauterine growth restriction. / Einstein, Francine; Thompson, Reid F.; Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit K.; Barzilai, Nir; Greally, John M.

In: PLoS One, Vol. 5, No. 1, e8887, 26.01.2010.

Research output: Contribution to journalArticle

Einstein, Francine ; Thompson, Reid F. ; Bhagat, Tushar D. ; Fazzari, Melissa J. ; Verma, Amit K. ; Barzilai, Nir ; Greally, John M. / Cytosine methylation dysregulation in neonates following intrauterine growth restriction. In: PLoS One. 2010 ; Vol. 5, No. 1.
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