人类植入前胚胎的DNA甲基化动态
Zachary D Smith1, Michelle M Chan2, Kathryn C Humm3
11] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA [3] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA [4] Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA [5].
Nature
|August 1, 2014
概括
哺乳动物的父基因组在早期发育过程中经历脱甲基化,人类研究显示,与小鼠相比,表观遗传调节保持和分化,特别是在基因体和物种特异性促进体中.
科学领域:
- 表观遗传学和发育生物学
- 基因组学和生物信息学
背景情况:
- 哺乳动物DNA甲基化通常在CpG位点稳定,与受精后父亲基因组的动态重编程形成鲜明对比.
- 虽然小鼠脱甲基化得到了很好的研究,但人类早期胚胎表观遗传景观需要直接测量进行比较分析.
研究的目的:
- 为了生成基因组规模的DNA甲基化地图的人类植入前发育和胚胎干细胞衍生.
- 将人类表观遗传重编程与已建立的小鼠模型进行比较,并确定保存和分离的特征.
主要方法:
- 基因组规模的DNA甲基化映射
- 对人类植入前胚胎和胚胎干细胞的分析.
- 用小鼠模型进行比较基因组学.
主要成果:
- 人类早期发育表现出暂时的全球低甲基化,其余甲基化维护主要在基因体中.
- 母性甲基化向人类的特定物种CpG岛屿促进体,与已知的小鼠印记不同.
- 逆转移素调节表现出多样性,母体到胚胎表达模式的变化.
结论:
- 父亲基因组去甲基化是哺乳动物早期发育的一个保留特征.
- 人类和小鼠的早期胚胎表观遗传景观显示了既保留的动态,也显示了特定物种的监管分歧.
- 独特的表观遗传调节模式是哺乳动物之间父性基因组重编程的特征.
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