Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues

Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprin...

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Main Authors:	Murphy, Susan K., Huang, Zhiqing, Hoyo, Cathrine
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396645/

id	pubmed-3396645
recordtype	oai_dc
spelling	pubmed-33966452012-07-17 Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Research Article Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure. Public Library of Science 2012-07-13 /pmc/articles/PMC3396645/ /pubmed/22808284 http://dx.doi.org/10.1371/journal.pone.0040924 Text en Murphy et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine
spellingShingle	Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
author_facet	Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine
author_sort	Murphy, Susan K.
title	Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
title_short	Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
title_full	Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
title_fullStr	Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
title_full_unstemmed	Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues
title_sort	differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues
description	Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396645/
_version_	1611543093642788864

Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues

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