2011 Fiscal Year Final Research Report
Genome-wide promoter methylation patterns are altered by a food component, genistein, during embryonic stem cell differentiation
| Project/Area Number |
22659070
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Human genetics
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SATO Noriko 東京医科歯科大学, 難治疾患研究所, 准教授 (70280956)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 環境感受性 / 胎内環境 / DNAメチル化-脱メチル化 / 着床期 |
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| Research Abstract |
Environmental challenges during development affect the fetal epigenome, but the period(s) vulnerable to epigenetic dysregulation are not clear. By employing a soy phytoestrogen, genistein, that is known to alter the epigenetic states of the Avy 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.
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