DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
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DOI：
10.1371/journal.pone.0026052
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Aburatani H
中科院分区：
文献类型：
--
作者：
Isagawa T;Nagae G;Shiraki N;Fujita T;Sato N;Ishikawa S;Kume S;Aburatani H
胚胎发生受到多种水平的表观遗传调控，如DNA甲基化、组蛋白修饰和染色质重塑。DNA甲基化模式在原始生殖细胞和受精后立即消失。随后的发育重编程通过从头甲基化和去甲基化发生。DNA甲基化模式在不同细胞类型之间的差异尚不清楚。在这里，我们利用甲基化DNA免疫沉淀法和瓦片阵列技术，全面分析了小鼠胚胎干细胞（ES）细胞、ES细胞衍生的早期生殖层（外胚层、内胚层和中胚层）和四个成体组织（脑、肝、骨骼肌和精子）近端启动子区域的DNA甲基化模式。大多数甲基化区域在所有三个胚层和三个成年体细胞组织中都被甲基化。这种常见的甲基化基因集在生殖细胞相关基因中富集，这些基因通常在体细胞中转录不活跃。我们还通过组蛋白H3赖氨酸4/27三甲基化的全局定位比较了DNA甲基化模式，发现DNA甲基化的获得与组蛋白H3赖氨酸4三甲基化的缺失相关。我们的综合研究结果表明，胚胎干细胞向三种生殖层的分化伴随着常见甲基化DNA区域数量的增加，并且这些甲基化的组织特异性改变仅发生在少数基因上。因此，DNA甲基化在常见甲基化基因的近端启动子区域似乎是一个不可逆的标记，其功能是通过抑制生殖细胞特异性基因的转录来固定体细胞谱系。
Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.
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影响因子：
4.8
作者：
Kawaguchi, Masahumi;Toyama, Tomoko;Yagi, Takeshi
通讯作者：
Yagi, Takeshi
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Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
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Surani MA
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1.9
作者：
Gottardo, Raphael;Li, Wei;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
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作者：
Farthing CR;Ficz G;Ng RK;Chan CF;Andrews S;Dean W;Hemberger M;Reik W
通讯作者：
Reik W
影响因子：
64.8
作者：
Boyer, LA;Plath, K;Jaenisch, R
通讯作者：
Jaenisch, R