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哺乳动物发育早期的基因组变异H3K4me3的基因重编程

Bingjie Zhang¹, Hui Zheng¹, Bo Huang^1,2

¹Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

|September 15, 2016

概括

像H3K4me3这样的基因组修饰在哺乳动物早期的发育过程中被重新编程. 卵细胞中的新型H3K4me3被遗传和删除,显示出动态表观遗传.

科学领域:

表观遗传学
发育生物学
基因组学

背景情况:

基因组修饰是控制细胞过程的关键表观遗传调节剂.
哺乳动物中基因素标记的跨代遗传性尚不清楚.
H3K4me3 是与转录启动相关的关键组织蛋白标记.

研究的目的:

在早期哺乳动物发育过程中研究H3K4me3的外观和遗传.
描述卵细胞中的新型H3K4me3及其动态.
了解受精后的基因质标记的重新编程.

主要方法:

开发一种敏感的方法,STAR ChIP-seq,用于分析H3K4me3.
在发育性子细胞,胚胎和植入前胚胎中分析H3K4me3模式.
研究细胞转录和DNA复制在H3K4me3删除中的作用.
涉及KDM5B的功能研究,以评估H3K4me3在基因组沉默中的作用.

主要成果:

在受精后对父亲H3K4me3进行了广泛的重编程,在胚胎细胞中减少并在晚期的双细胞阶段重新建立.
在卵细胞中发现非正规的H3K4me3 (ncH3K4me3),其特征是促进体和远端位置的广泛峰值,与部分甲基化DNA域重叠.
在植入前胚胎中遗传ncH3K4me3,然后在晚期的双细胞胚胎中删除.
删除ncH3K4me3需要细胞转录,而不是通过DNA复制被动稀释.
卵细胞中H3K4me3的下调导致基因组沉默的缺陷.

结论:

哺乳动物的配体表现出动态表观遗传重新编程的基因素标记,包括H3K4me3.
卵细胞中的新型H3K4me3在早期发育中起作用,并受到动态除.
这些发现提供了关于哺乳动物早期发育过程中的表观基因组遗传和重编程的见解.

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