人类早期胚胎中的染色质可访问性景观及其与进化相关性
Lei Gao1, Keliang Wu2, Zhenbo Liu1
1CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China.
Cell
|March 13, 2018
概括
在人类早期发育过程中建立了染色质的可访问性,OCT4在胚胎基因组激活 (ZGA) 中发挥了关键作用. 基因年龄和转子子活动也会影响早期胚胎的基因表达动态.
科学领域:
- 发育生物学
- 表观遗传学
- 基因组学
背景情况:
- 在早期人类胚胎发生过程中,染色质调节的作用在很大程度上还未被探索.
- 了解基因调节的动态对于发育过程至关重要.
研究的目的:
- 研究人类早期胚胎形成过程中的染色质可访问性.
- 探索 OCT4 等转录因子在早期发育和胚胎基因组激活 (ZGA) 中的作用.
- 了解基因年龄,促进体特征和表达时间之间的关系.
主要方法:
- 用DNase I过敏部位 (DHS) 测序来绘制染色体可访问性的地图.
- 对OCT4结合基因及其丰富性的分析.
- 基因年龄和促进物CpG含量与DHS建立和基因表达的相关性.
主要成果:
- 在人类早期胚胎形成过程中,染色质的可获得性逐渐建立.
- 在人体中,OCT4结合基因在ZGA中得到丰富,OCT4对人类ZGA至关重要,与小鼠不同.
- 较年轻的基因和较低CpG促进体的基因与较晚的DHS建立和表达有关,而较老的基因则显示较早的模式.
- 活跃的人类转体子 (SVA,HERV-K) 携带DHS,在早期胚胎中表达,但不在分化组织中表达.
结论:
- 这项研究揭示了在人类早期发育过程中染色体景观的动态建立.
- 在ZGA中OCT4的物种特异性作用突出了发育调节的进化差异.
- 基因年龄和转子子活动是胚胎发生过程中调节基因和转子表达的重要因素,提供了进化发展的视角.
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