genome-wide dna methylation analysis reveals phytoestrogen modification of promoter methylation patterns during embryonic stem cell differentiation全基因组dna甲基化分析揭示了植物雌激素修改启动子甲基化模式在胚胎干细胞分化.pdfVIP

genome-wide dna methylation analysis reveals phytoestrogen modification of promoter methylation patterns during embryonic stem cell differentiation全基因组dna甲基化分析揭示了植物雌激素修改启动子甲基化模式在胚胎干细胞分化.pdf

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genome-wide dna methylation analysis reveals phytoestrogen modification of promoter methylation patterns during embryonic stem cell differentiation全基因组dna甲基化分析揭示了植物雌激素修改启动子甲基化模式在胚胎干细胞分化

Genome-Wide DNA Methylation Analysis Reveals Phytoestrogen Modification of Promoter Methylation Patterns during Embryonic Stem Cell Differentiation 1 2 1 3 4 1 Noriko Sato *, Naomi Yamakawa , Moe Masuda , Katsuko Sudo , Izuho Hatada , Masaaki Muramatsu 1 Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan, 2 Research Team for Geriatric Disease, Institute of Gerontology and Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, 3 Animal Research Center, Tokyo Medical University, Tokyo, Japan, 4 Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan Abstract Background: 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 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. Methods and Findings: 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 a

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