在小鼠卵细胞中,广泛的素H3K4me3域调节母体到胚胎的过渡
John Arne Dahl1, Inkyung Jung2, Håvard Aanes1
1Department of Microbiology, Oslo University Hospital, Rikshospitalet, NO-0027 Oslo, Norway.
Nature
|September 15, 2016
概括
孕产妇转化为胚胎的过程 (MZT) 涉及动态的基因质变化. 新的微量ChIP-seq揭示了卵细胞中的广泛H3K4me3域对于胚胎基因组激活和早期胚胎发育至关重要.
科学领域:
- 发育生物学
- 表观遗传学
- 基因组学
背景情况:
- 对于启动胚胎发育而言,母体转化至胚胎转化 (MZT) 是至关重要的,但仍然不太清楚.
- 由于细胞数量有限,在MZT期间直接测量染色质状态具有挑战性.
- 在MZT中涉及质子修饰,但它们的确切作用和动态尚不清楚.
研究的目的:
- 开发和应用微量染色体免疫沉和测序 (μChIP-seq) 方法,用于早期小鼠胚胎中的基因组修饰.
- 在MZT过程中研究基因组H3 lysine甲基化 (H3K4me3) 和乙化 (H3K27ac) 的分布和动态.
- 阐明特定基因组修饰在胚胎基因组激活和早期胚胎发育中的作用.
主要方法:
- 开发一个微量染色体免疫沉和测序 (μChIP-seq) 试验,从小细胞数量中进行分析.
- 在小鼠卵细胞 (未成熟和第II阶段) 和早期胚胎 (2细胞和8细胞阶段) 中对全基因组H3K4me3和H3K27ac进行分析.
- 在MZT过程中对基因修饰,DNA甲基化和基因表达之间的关系进行分析.
主要成果:
- 大约22%的卵细胞基因组表现出广泛的H3K4me3域,与DNA甲基化相反相关.
- 在二细胞胚胎中,H3K4me3域从广泛的模式过渡到转录起点特定的定位,同时与胚胎基因组激活.
- 通过KDM5A和KDM5B进行广泛的H3K4me3域的活性去除对于正常的胚胎基因组激活和随后的发育至关重要.
结论:
- 卵细胞中广泛的H3K4me3域在调节母体转化为胚胎的过程中起着重要作用.
- H3K4me3的动态调节,特别是其通过KDM5A/B的去除,对于成功的胚胎基因组激活和早期小鼠胚胎发育至关重要.
- 开发的μChIP-seq方法为在发育过程中有限的细胞群体的表观遗传动力学提供了强大的工具.
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