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Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors

Novakovic, Boris, Yuen, Ryan K, Gordon, Lavinia, Penaherrera, Maria S, Sharkey, Andrew, Moffett, Ashley, Craig, Jeffrey M, Robinson, Wendy P and Saffery, Richard 2011, Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors, BMC genomics, vol. 12, pp. 1-14, doi: 10.1186/1471-2164-12-529.

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Title Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors
Author(s) Novakovic, Boris
Yuen, Ryan K
Gordon, Lavinia
Penaherrera, Maria S
Sharkey, Andrew
Moffett, Ashley
Craig, Jeffrey M
Robinson, Wendy P
Saffery, Richard
Journal name BMC genomics
Volume number 12
Article ID 529
Start page 1
End page 14
Total pages 14
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2011-10-28
ISSN 1471-2164
Keyword(s) methylation level
ingenuity pathway analysis
human placenta
trimester placenta
circadian rhythm signalling
science & technology
life sciences & biomedicine
biotechnology & applied microbiology
genetics & heredity
Summary BACKGROUND: The human placenta facilitates the exchange of nutrients, gas and waste between the fetal and maternal circulations. It also protects the fetus from the maternal immune response. Due to its role at the feto-maternal interface, the placenta is subject to many environmental exposures that can potentially alter its epigenetic profile. Previous studies have reported gene expression differences in placenta over gestation, as well as inter-individual variation in expression of some genes. However, the factors contributing to this variation in gene expression remain poorly understood.

RESULTS: In this study, we performed a genome-wide DNA methylation analysis of gene promoters in placenta tissue from three pregnancy trimesters. We identified large-scale differences in DNA methylation levels between first, second and third trimesters, with an overall progressive increase in average methylation from first to third trimester. The most differentially methylated genes included many immune regulators, reflecting the change in placental immuno-modulation as pregnancy progresses. We also detected increased inter-individual variation in the third trimester relative to first and second, supporting an accumulation of environmentally induced (or stochastic) changes in DNA methylation pattern. These highly variable genes were enriched for those involved in amino acid and other metabolic pathways, potentially reflecting the adaptation of the human placenta to different environments.

CONCLUSIONS: The identification of cellular pathways subject to drift in response to environmental influences provide a basis for future studies examining the role of specific environmental factors on DNA methylation pattern and placenta-associated adverse pregnancy outcomes.
Language eng
DOI 10.1186/1471-2164-12-529
Field of Research 06 Biological Sciences
11 Medical And Health Sciences
08 Information And Computing Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2011, Novakovic et al
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30110736

Document type: Journal Article
Collections: School of Medicine
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