2019年7月26日出版的《科学》杂志发表了中国科学家的一项最新研究成果。来自清华大学和郑州大学第一附属医院的科学家合作探明了人类从亲本到合子的转变过程中组蛋白修饰重编程。

为了研究组蛋白修饰在人类早期发育过程中是如何被重新编程的，课题组研究了人类卵母细胞和早期胚胎中的关键组蛋白标记。与小鼠卵母细胞不同的是，人类卵母细胞中允许标记三甲基化组蛋白H3赖氨酸4 (H3K4me3)，这在启动子上表现出规范化模式。受精后，prezygotic genome activation（pre-ZGA）胚胎在CpG丰富调控区域获得允许的染色质和广泛分布的H3K4me3。相比之下，抑制性标记H3K27me3经历全基因组丢失。富含CpG的调控区域在ZGA上分解为活性或抑制状态，随后在发育基因上恢复H3K27me3。最后，通过结合染色质和转录组图谱，研究人员揭示了早期谱系规范期间的转录线路和不对称H3K27me3模式。总的来说，研究数据揭示了一个启动阶段，连接着人类亲本到合子的表观基因组转换。

研究人员表示，组蛋白修饰起着调节基因的表达与发育的重要作用。

附：英文原文

Title: Resetting histone modifications during human parental-to-zygotic transition

Author: Weikun Xia, Jiawei Xu, Guang Yu, Guidong Yao, Kai Xu, Xueshan Ma, Nan Zhang, Bofeng Liu, Tong Li, Zili Lin, Xia Chen, Lijia Li, Qiujun Wang, Dayuan Shi, Senlin Shi, Yile Zhang, Wenyan Song, Haixia Jin, Linli Hu, Zhiqin Bu, Yang Wang, Jie Na, Wei Xie, Ying-Pu Sun

Issue&Volume: Vol 365 Issue 6451

Abstract: Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse oocytes, the permissive mark trimethylated histone H3 lysine 4 (H3K4me3) largely exhibits canonical patterns at promoters in human oocytes. After fertilization, prezygotic genome activation (pre-ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, by combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition.

DOI: 10.1126/science.aaw5118

Source:https://science.sciencemag.org/content/365/6451/353