母体H3K27me3控制了DNA甲基化独立的印记
Azusa Inoue1,2,3, Lan Jiang1,2,3, Falong Lu1,2,3
1Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|July 21, 2017
概括
这项研究揭示了哺乳动物的新型DNA甲基化独立印记机制. 孕产妇基因素H3 lysine 27三甲基化 (H3K27me3) 控制了印记基因表达,特别是在胚胎外的组织中.
科学领域:
- 表观遗传学
- 基因组学
- 发育生物学
背景情况:
- 哺乳动物的精子和卵细胞具有不同的表观遗传特征.
- 在受精后,除了印记控制区域外,父母表观基因组在很大程度上均等.
- 表观遗传平衡和印记逃脱的机制仍然不太清楚.
研究的目的:
- 研究调控亲代基因特异性染色体可访问性的表观遗传机制.
- 识别DNA甲基化之外的新型印记机制.
- 了解印记控制区域如何逃避重新编程.
主要方法:
- 在小鼠生殖细胞和毛囊胚胎中对父基因特异性DNase I过敏位点进行分析.
- 对DNA甲基组和H3K27me3染色体免疫沉的综合分析,然后进行测序.
- 研究H3K27me3在印记中的功能作用.
主要成果:
- 鉴定了76个具有父方等位基因特异性DNase I过敏位点的基因,缺乏DNA甲基化,但对母方H3K27me3进行了丰富.
- 这些基因在植入前胚胎中以父式方式表达.
- 宫外H3K27me3的去除触发了母体的等位基因表达,表明H3K27me3的调节作用.
- 在胚胎血统中,H3K27me3依赖印记大多会消失,但在胚胎外的血统中至少保留了5个基因.
结论:
- 母体H3K27me3作为DNA甲基化独立的印记机制.
- 这种机制对于调节印制基因表达至关重要,特别是在胚胎外的组织中.
- 鉴定了关键基因,在胚胎外的血统中保持印记,独立于卵细胞DNA甲基化.
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