Genomics

Dataset Information

0

Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome


ABSTRACT: Environmental factors during perinatal development influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring perinatally exposed to multiple doses of BPA through the maternal diet. Using a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 µg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N=4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response. In this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways were identified and validated. The comprehensive methylome map presented here provides candidate loci underlying the role of early BPA exposure and later in life health and disease status. For this study, liver DNA from a subset of a/a wild-type animals was analyzed for full methylome characteristics: 1) standard diet (Ctr, n = 4 offspring; 2 male and 2 female); 2) 50 µg BPA/kg diet (UG, n = 4 offspring; 2 male and 2 female); 3) 50 mg BPA/kg diet (MG, n = 4 offspring; 1 male and 3 female).

ORGANISM(S): Mus musculus  

SUBMITTER: Jung Kim  Maureen A Sartr   Christopher Faulk   Olivia S Anderson   Muna S Nahar   Tami R Jones   Laura S Rozek   Dana C Dolinoy   Jung H Kim    

PROVIDER: E-GEOD-46183 | ArrayExpress | 2013-11-17

SECONDARY ACCESSION(S): GSE46183SRP021181PRJNA198014

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications

Sorry, this publication's infomation has not been loaded in the Indexer, please go directly to PUBMED or Altmetric.

Similar Datasets

2013-08-13 | E-GEOD-49797 | ArrayExpress
2016-03-26 | E-GEOD-57005 | ArrayExpress
2013-06-01 | E-GEOD-43038 | ArrayExpress
2016-02-25 | E-GEOD-76012 | ArrayExpress
2011-06-01 | E-MEXP-3205 | ArrayExpress
2018-01-29 | PXD001540 | Pride
2013-11-27 | E-GEOD-46359 | ArrayExpress
2013-09-09 | E-GEOD-45607 | ArrayExpress
2009-10-01 | E-MEXP-1909 | ArrayExpress
2014-01-21 | E-GEOD-44901 | ArrayExpress