Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Estrogen Induced DNA Methylation Changes in Mouse Hippocampus

ABSTRACT: Estrogen, specifically estradiol, has been shown to mediate DNA methylation changes at mutiple locations downstream of estrogen response elements (EREs). We identified differentially methylated regions associated with long-term estradiol exposure in the hippocampus of C57BL/6J mice. Hippocampus was collected from ovariectomized (OVX) C57BL/6J mice treated with estradiol (n=5) and vehicle controls (n=5). Genomic DNA was extracted and treated with methylation sensitive restriction enzymes HpaII and HinP1I to enrich for the unmethylated fraction. This fraction was interrogated using the Affymetrix GeneChip® Mouse Tiling Promoter 1.0R Array

ORGANISM(S): Mus musculus

SUBMITTER: Jerry Guintivano

PROVIDER: E-GEOD-43460 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Antenatal prediction of postpartum depression with blood DNA methylation biomarkers.

Guintivano J J Arad M M Gould T D TD Payne J L JL Kaminsky Z A ZA

Molecular psychiatry 20130521 5

Postpartum depression (PPD) affects ∼10-18% of women in the general population and results in serious consequences to both the mother and offspring. We hypothesized that predisposition to PPD risk is due to an altered sensitivity to estrogen-mediated epigenetic changes that act in a cell autonomous manner detectable in the blood. We investigated estrogen-mediated epigenetic reprogramming events in the hippocampus and risk to PPD using a cross-species translational design. DNA methylation profile ...[more]

PMID: 23689534

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Project description:Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation. Experiment Overall Design: We used oligonucleotide expression microarrays (Affymetrix GeneChip U133 Plus 2.0) to identify estradiol (E2)-responsive genes in the estrogen-receptor positive breast cancer cell line, MCF7. MCF7 cells were grown to 30-50% confluency and exposed to 10 nM E2 (or vehicle only) at 12, 24, and 48 hours. Each timepoint was performed in triplicate (ie, biological replicates). Total RNA was isolated from cells using the Qiagen RNeasy kit, and 5 micrograms of total RNA was amplified, labeled and hybridized to the array according to the manufacturerâs protocols.

Dataset Information

Estrogen Induced DNA Methylation Changes in Mouse Hippocampus

Publications

Antenatal prediction of postpartum depression with blood DNA methylation biomarkers.

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