Genome-wide promoter methylation patterns are altered by a food component, genistein, during embryonic stem cell differentiation

在胚胎干细胞分化过程中，食物成分金雀异黄素改变了全基因组启动子甲基化模式

• 批准号: 22659070
• 负责人: SATO Noriko
• 金额: $ 1.92万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659070/
• 关键词: 環境感受性; 胎内環境; DNAメチル化-脱メチル化; 着床期; エピゲノム; 子宮内環境; 新生DNAメチル化; DNA脱メチル化; DNAメチル化

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.

发育过程中的环境挑战会影响胎儿表观基因组，但易受表观遗传失调影响的时期尚不清楚。通过使用大豆植物雌激素金雀异黄酮（已知它可以在胚胎发生过程中改变 Avy 等位基因的表观遗传状态），我们探索了表观遗传调控的敏感期。植入后时期，DNA 从头甲基化活跃进行，适合使用小鼠胚胎干 (ES) 细胞分化系统进行体外分析。小鼠 ES 细胞在金雀异黄素存在或不存在的情况下进行分化，并通过基于微阵列的启动子甲基化分析结合甲基化敏感核酸内切酶 (HpaII/McrBC) 依赖性富集程序来比较第 10 天的 DNA 甲基化模式。在金雀异黄素处理后，在启动子子集中观察到甲基化水平的适度变化。对 Ucp1 和 Sytl1 启动子的详细研究进一步表明，金雀异黄素不会影响第 0 天和第 4 天之间发生的从头甲基化，但会干扰后续的调控过程并导致两个启动子的甲基化水平降低。金雀异黄素扰乱分化 ES 细胞从头甲基化后的甲基化模式。我们的观察表明，对于一部分基因来说，早期胚胎中 DNA 从头甲基化后的调控可能对金雀异黄素敏感。

项目成果

DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.

• DOI: 10.1371/journal.pone.0026052
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H
• 通讯作者: Aburatani H

Effects of Maternal Low Protein Diet on Methylation Variation in Leptin Promoter

母亲低蛋白饮食对瘦素启动子甲基化变异的影响

• 发表时间: 2011
• 作者: Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H;Matsukura H;Sato N;Sato N
• 通讯作者: Sato N

Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

金雀异黄素促进子宫内膜基质细胞中类固醇生成因子 1 (SF-1) 启动子的 DNA 去甲基化

• DOI: 10.1016/j.bbrc.2011.07.104
• 发表时间: 2011
• 期刊: Biochem Biophys Res Commun
• 作者: Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H;Matsukura H
• 通讯作者: Matsukura H

ES細胞分化過程においてゲニステインがDNAメチル化状態に与える影響の解析

金雀异黄素对ES细胞分化过程中DNA甲基化状态的影响分析

• 发表时间: 2010
• 作者: Isagawa;T;et al.;佐藤憲子
• 通讯作者: 佐藤憲子

Alteration of Ucp1 Promoter Methylation by Phytoestrogen in Mouse Embryoid Body Differentiation Culture

小鼠胚体分化培养中植物雌激素对 Ucp1 启动子甲基化的改变

• 发表时间: 2011
• 作者: Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H;Matsukura H;Sato N
• 通讯作者: Sato N