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人类早期发育中的染色体分析显示ZGA期间的表观遗传转变

Jingyi Wu^1,2,3, Jiawei Xu⁴, Bofeng Liu¹

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, China.

|May 4, 2018

概括

人类早期胚胎在基因组激活之前显示广泛可访问的染色体. 这种染色体景观在胚胎基因组激活 (ZGA) 过程中经历了显著的重组,这是一个影响表观遗传重编程的保存哺乳动物过程.

科学领域:

发育生物学
表观遗传学
基因组学

背景情况:

在早期胚胎发育过程中,染色质重组至关重要.
在人类植入前的发展过程中,全球的染色体格局在很大程度上是未知的.
了解人类早期发育中的表观遗传编程至关重要.

研究的目的:

研究人类植入前发育过程中的染色质状态和分子动力学.
在胚胎基因组激活 (ZGA) 之前和之后探索染色质的可访问性.
为了比较人类和小鼠早期发育之间的调节电路.

主要方法:

使用了一种改进的转化酶可访问的高通量测序 (ATAC-seq) 染色体检测方法.
进行了染色体状态,Cis调节序列和可转移元素的整合性分析.
检查了包括H3K4me3和DNA甲基化模式在内的基因素修饰.

主要成果:

在早期人类胚胎中确定了广泛的可访问的染色体区域,与调控元素和可转移元素重叠.
在胚胎基因组激活 (ZGA) 之前观察到广泛的开放色素,许多区域位于距离区域和DNA低甲基域.
证明可访问的染色体区域在ZGA后以转录依赖的方式变得很大程度上无法访问,这是与H3K4me3重编程相关的保存过程.

结论:

在哺乳动物ZGA期间发现了保存的染色体过渡原理.
对人类早期发育和体外受精中的表观遗传重编程的高级理解.
突出了早期胚胎形成过程中染色质可访问性及其调节的动态性质.

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