Chu, T and Handley, D and Bunce, K and Surti, U and Hogge, WA and Peters, DG
(2011)
Structural and regulatory characterization of the placental epigenome at its maternal interface.
PLoS ONE, 6 (2).
Abstract
Epigenetics can be loosely defined as the study of cellular "traits" that influence biological phenotype in a fashion that is not dependent on the underlying primary DNA sequence. One setting in which epigenetics is likely to have a profound influence on biological phenotype is during intrauterine development. In this context there is a defined and critical window during which balanced homeostasis is essential for normal fetal growth and development. We have carried out a detailed structural and functional analysis of the placental epigenome at its maternal interface. Specifically, we performed genome wide analysis of DNA methylation in samples of chorionic villus (CVS) and maternal blood cells (MBC) using both commercially available and custom designed microarrays. We then compared these data with genome wide transcription data for the same tissues. In addition to the discovery that CVS genomes are significantly more hypomethylated than their MBC counterparts, we identified numerous tissue-specific differentially methylated regions (T-DMRs). We further discovered that these T-DMRs are clustered spatially along the genome and are enriched for genes with tissue-specific biological functions. We identified unique patterns of DNA methylation associated with distinct genomic structures such as gene bodies, promoters and CpG islands and identified both direct and inverse relationships between DNA methylation levels and gene expression levels in gene bodies and promoters respectively. Furthermore, we found that these relationships were significantly associated with CpG content. We conclude that the early gestational placental DNA methylome is highly organized and is significantly and globally associated with transcription. These data provide a unique insight into the structural and regulatory characteristics of the placental epigenome at its maternal interface and will drive future analyses of the role of placental dysfunction in gestational disease. © 2011 Chu et al.
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| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
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| Centers: |
Other Centers, Institutes, Offices, or Units > Center for Bioengineering |
| Date: |
2 March 2011 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
6 |
| Number: |
2 |
| DOI or Unique Handle: |
10.1371/journal.pone.0014723 |
| Refereed: |
Yes |
| MeSH Headings: |
Chorionic Villi--metabolism; CpG Islands; DNA Methylation; Epigenesis, Genetic--physiology; Epigenomics--methods; Erythrocytes--metabolism; Female; Gene Expression Profiling; Gene Expression Regulation; Genes; Genome, Human; Humans; Oligonucleotide Array Sequence Analysis; Placenta--metabolism; Pregnancy; Pregnancy Trimester, First--blood; Pregnancy Trimester, First--genetics; Pregnancy Trimester, First--metabolism; Regulatory Sequences, Nucleic Acid--genetics |
| Other ID: |
NLM PMC3044138 |
| PubMed Central ID: |
PMC3044138 |
| PubMed ID: |
21373191 |
| Date Deposited: |
07 Aug 2012 15:51 |
| Last Modified: |
02 Feb 2019 14:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13420 |
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