哺乳动物中父母DNA甲基组的编程和遗传
Lu Wang1,2, Jun Zhang3, Jialei Duan1
1CAS Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing 100101, China.
Cell
|May 13, 2014
概括
父母DNA甲基化模式在胚胎早期发育过程中经历活跃脱甲基化,而不仅仅是被动稀释. 这种积极的重新编程对于开发和印记控制至关重要.
科学领域:
- 表观遗传学和发育生物学
- 基因组印记是一种基因组印记.
- DNA 甲基化动力学
背景情况:
- 父母甲基组重编程对于哺乳动物胚胎发育至关重要.
- 以前的假设表明,父性5-甲基细胞素 (5mC) 氧化和甲基基的被动稀释.
研究的目的:
- 研究父亲和母亲甲基组重编程的机制.
- 确定活性脱甲基化与被动稀释在早期胚胎发生过程中的作用.
- 绘制氧化细胞因子基的地图,并对印记控制区域 (ICR) 进行分类.
主要方法:
- 产生单基分辨率,来自小鼠体,早期胚胎和原始生殖细胞 (PGC) 的等位基特异性DNA甲基组.
- 在早期胚胎中创建氧化细胞因子基 (5hmC,5fC) 的单基分辨率图.
主要成果:
- 在母体和父体基因组中确定了5-基甲基氨酸 (5hmC) 和5-甲基氨酸 (5fC).
- 在大多数脱甲基化CpG中,证明了5mC或其氧化衍生物的转化为未经修改的细胞因子,独立于被动稀释.
- 将所有已知的印记控制区域 (ICR) 分类为生殖系或体型.
结论:
- 在胚胎发育过程中,父亲甲基组和母亲甲基组的很大一部分经历了活性脱甲基化.
- 主动去甲基化,而不是仅仅是被动稀释,是甲基组重编程的主要机制.
- 研究结果提供了对表观遗传和印记的精确控制的见解.
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