Longitudinal Effects of Developmental Bisphenol A Exposure on Epigenome-Wide DNA Hydroxymethylation at Imprinted Loci in Mouse Blood

Epigenetic machinery plays an important role in genomic imprinting, a developmental process that establishes parent-of-origin-specific monoallelic gene expression. Although a number of studies have investigated the role of 5-methylcytosine in imprinting control, the contribution of 5-hydroxymethylcy...

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Bibliographic Details
Published in:Environmental health perspectives 2018-07, Vol.126 (7), p.077006
Main Authors: Kochmanski, Joseph J, Marchlewicz, Elizabeth H, Cavalcante, Raymond G, Perera, Bambarendage P U, Sartor, Maureen A, Dolinoy, Dana C
Format: Article
Language:English
Subjects:
5-Methylcytosine - analogs & derivatives
5-Methylcytosine - metabolism
Animals
Benzhydryl Compounds - adverse effects
Bioinformatics
Bisphenol A
Blood
Brain research
Cell growth
Deoxyribonucleic acid
Diet
DNA
DNA methylation
DNA sequencing
Environmental Pollutants - adverse effects
Epigenesis, Genetic - drug effects
Epigenetic inheritance
Epigenetics
Exposure
Female
Gene expression
Gene Expression Regulation, Developmental - drug effects
Gene regulation
Genes
Genomes
Genomic imprinting
Hypotheses
Immunoprecipitation
KCNQ1 protein
Laboratory animals
Loci
Male
Methylation
Mice
Oxidative stress
Perinatal exposure
Phenols
Phenols - adverse effects
Phosphodiesterase
Potassium channels (voltage-gated)
Stem cells
Studies
Toxicants
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Summary:Epigenetic machinery plays an important role in genomic imprinting, a developmental process that establishes parent-of-origin-specific monoallelic gene expression. Although a number of studies have investigated the role of 5-methylcytosine in imprinting control, the contribution of 5-hydroxymethylcytosine (5-hmC) to this epigenetic phenomenon remains unclear. Using matched mouse blood samples (from mice at 2, 4, and 10 months of age), our objective was to examine the effects of perinatal bisphenol A (BPA) exposure (50 μg/kg diet) on longitudinal 5-hmC patterns at imprinted regions. We also aimed to test the hypothesis that 5-hmC would show defined patterns at imprinted genes that persist across the life course. Genome-wide 5-hmC levels were measured using hydroxymethylated DNA immunoprecipitation sequencing (HMeDIP-seq). Modeling of differential hydroxymethylation by BPA exposure was performed using a pipeline of bioinformatics tools, including the R package. Based on BPA exposure, we identified 5,950 differentially hydroxymethylated regions (DHMRs), including 12 DHMRs that were annotated to murine imprinted genes— , , , , , , , , , , and . When visualized, these imprinted gene DHMRs showed clear, consistent patterns of differential 5-hmC by developmental BPA exposure that persisted throughout adulthood. These data show long-term establishment of 5-hmC marks at imprinted loci during development. Further, the effect of perinatal BPA exposure on 5-hmC at specific imprinted loci indicates that developmental exposure to environmental toxicants may alter long-term imprinted gene regulation via an epigenetic mechanism. https://doi.org/10.1289/EHP3441.
ISSN:0091-6765
1552-9924
DOI:10.1289/EHP3441