A restricted repertoire of cytosine methylation changes in neonates following intrauterine growth restriction
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ABSTRACT: 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 sometimes decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations. Our studies focused specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood, and 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 intrauterine growth restriction (IUGR), but that they are of a substantially lesser degree and involve many fewer loci than the epigenomic dysregulation observed in cancer. This is consistent with a comparable study of individuals born following maternal starvation during the Dutch famine. 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. Our results give some insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. Direct comparison of DNA methylation in 10 neonatal CD34+ samples isolated from umbilical cord blood belonging to two groups: IUGR (n=5) and their age-matched controls (n=5). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).
ORGANISM(S): Homo sapiens
SUBMITTER: Amit Verma
PROVIDER: E-GEOD-17727 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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