在胚胎干细胞中对5-基甲基细胞素的全基因组映射
William A Pastor1, Utz J Pape, Yun Huang
1Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Nature
|May 10, 2011
概括
这项研究引入了新的方法,可以在整个基因组中绘制5-基甲基细胞素 (5hmC) 的地图. 研究结果显示,在外原体和接近起始点的5hmC丰富,表明在胚胎干细胞中调节基因表达的作用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 5-基甲基细胞因子 (5hmC) 是一种由TET酶从5-甲基细胞因子 (5mC) 衍生出来的DNA修饰.
- 5hmC和TET蛋白与干细胞生物学和癌症有关.
- 目前,5hmC的全基因组分布数据有限.
研究的目的:
- 开发新的,特定的方法来分析5hmC.的基因组定位.
- 为了研究5hmC在小鼠胚胎干细胞中的全基因组分布.
- 阐明5hmC在转录调节和染色质状态中的潜在作用.
主要方法:
- 开发了两种新方法:GLIB (葡萄糖化,周期性氧化,生物化) 和二硫酸盐转化为氨酸5-甲基硫酸盐 (CMS),然后进行免疫沉.
- 来自小鼠ES细胞的5hmC丰富DNA的高通量测序.
- 分析5hmC分布与基因特征和基因素修饰相关的分析 (H3K27me3,H3K4me3).
主要成果:
- 发现5hmC在老鼠ES细胞的外显子和转录起点 (TSS) 附近被显著丰富.
- 在具有双重H3K27me3和H3K4me3标记的基因的起始部位观察到5hmC的特定丰富.
- 这项研究提供了第一个详细的5hmC分布的全基因组图.
结论:
- 5hmC可能在转录调节中发挥作用.
- 5hmC可能有助于ES细胞中发育调节基因中观察到的"平衡"色素特征.
- 开发的方法为未来对5hmC的表观基因组研究提供了强大的工具.
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