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Genome-wide DNA methylation analysis reveals phytoestrogen modification of promoter methylation patterns during embryonic stem cell differentiation

Environmental challenges during development affect the fetal epigenome, but the period(s) vulnerable to epigenetic dysregulation is(are) not clear. By employing a soy phytoestrogen, genistein, that is known to alter the epigenetic states of the A(vy) allele during embryogenesis, we have explored the...

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Published in:PloS one 2011-04, Vol.6 (4), p.e19278-e19278
Main Authors: Sato, Noriko, Yamakawa, Naomi, Masuda, Moe, Sudo, Katsuko, Hatada, Izuho, Muramatsu, Masaaki
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cited_by cdi_FETCH-LOGICAL-c691t-8064b1a1e2ee9f2cabf7dc9d79ae1a9f130d35b6cee232ff70f61c7612898cd93
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creator Sato, Noriko
Yamakawa, Naomi
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Muramatsu, Masaaki
description Environmental challenges during development affect the fetal epigenome, but the period(s) vulnerable to epigenetic dysregulation is(are) not clear. By employing a soy phytoestrogen, genistein, that is known to alter the epigenetic states of the A(vy) allele during embryogenesis, we have explored the sensitive period for epigenetic regulation. The post-implantation period, when de novo DNA methylation actively proceeds, is amenable to in vitro analysis using a mouse embryonic stem (ES) cell differentiation system. Mouse ES cells were differentiated in the presence or absence of genistein, and DNA methylation patterns on day 10 were compared by microarray-based promoter methylation analysis coupled with a methylation-sensitive endonuclease (HpaII/McrBC)-dependent enrichment procedure. Moderate changes in methylation levels were observed in a subset of promoters following genistein treatment. Detailed investigation of the Ucp1 and Sytl1 promoters further revealed that genistein does not affect de novo methylation occurring between day 0 and day 4, but interferes with subsequent regulatory processes and leads to a decrease in methylation level for both promoters. Genistein perturbed the methylation pattern of differentiated ES cells after de novo methylation. Our observations suggest that, for a subset of genes, regulation after de novo DNA methylation in the early embryo may be sensitive to genistein.
doi_str_mv 10.1371/journal.pone.0019278
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subjects Adipocytes
Analysis
Animals
Biology
Biosynthesis
Bisphenol A
Cell differentiation
Cell Differentiation - drug effects
Chemistry
CpG Islands
Critical period
Deoxyribonucleic acid
Differentiation (biology)
DNA
DNA - genetics
DNA Methylation
DNA microarrays
Embryogenesis
Embryonic growth stage
Embryonic stem cells
Embryonic Stem Cells - cytology
Endonuclease
Environment
Epidemiology
Epigenesis, Genetic
Epigenetic inheritance
Epigenetics
Fetuses
Gene expression
Gene regulation
Genes
Genetic testing
Genistein
Genistein - pharmacology
Genome
Genomes
Genomics
Geriatrics
Glycine max
Implantation
Isoflavones
Leukemia
Medical research
Medicine
Methylation
Mice
Mice, Inbred C57BL
Mitochondrial DNA
Phytoestrogens - metabolism
Promoter Regions, Genetic
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Science
Stem cells
title Genome-wide DNA methylation analysis reveals phytoestrogen modification of promoter methylation patterns during embryonic stem cell differentiation
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