RNA聚合酶I在小鼠胚胎早期发育过程中对3D基因组的形成起着至关重要的作用,而在人类胚胎早期发育过程中则没有作用。

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Changliang Hou, Geng G Tian, Shuanggang Hu, Beili Chen, Xiaoyong Li, Bo Xu, Yuedi Cao, Wei Le, Rong Hu, Hao Chen, Yan Zhang, Qian Fang, Man Zhang, Zhaoxia Wang, Zhiguo Zhang, Jinfu Zhang, Zhaolian Wei, Guangxin Yao, Yefan Wang, Ping Yin, Ya Guo, Guoqing Tong, Xiaoming Teng, Yun Sun, Yunxia Cao, Ji Wu
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引用次数: 0

摘要

背景:三维(3D)染色质结构在哺乳动物配子体发生和早期胚胎发生过程中经历了动态重组。虽然小鼠研究已经显示了物种特异性模式以及新生组织的机制,但这些在人类中仍然缺乏特征。尽管RNA聚合酶II和III已经被证明可以调节染色质结构,但在这些发育转变过程中,驱动核糖体RNA产生的RNA聚合酶I (Pol I)在塑造3D基因组组织中的潜在作用尚未被研究。方法:采用改进的低输入原位Hi-C方法,系统比较人类和小鼠配子体发生至早期胚胎发生的三维基因组结构动态。互补Smart-seq2用于低输入转录组学,CUT&Tag用于Pol I分析,Pol I功能抑制分析用于阐明染色质组织的调控机制。结果:我们的研究揭示了从人类卵发生到早期胚胎发生的3D基因组的广泛重组,显示出与小鼠的显著差异,包括在生发囊泡(GV)阶段卵母细胞的拓扑相关结构域(TADs)显着减弱。三维基因组重建的时间是物种之间的根本区别。在人类中,重构开始于4细胞期胚胎,而在小鼠中,重构开始于2细胞期胚胎。我们发现Pol I在小鼠胚胎发生过程中对染色质结构的建立至关重要,但在人类胚胎中没有。有趣的是,Pol I转录的缺失削弱了小鼠雌性生殖系干细胞的TAD结构,而在人类生殖系干细胞中却增强了TAD结构。结论:这些观察到的染色质组织动力学的物种间差异为早期哺乳动物发育中染色质结构调节的进化差异提供了新的见解。我们的发现为生殖细胞和胚胎发育过程中物种特异性染色质组织的机制提供了见解,并对生育能力的保存和出生缺陷的预防具有潜在的意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
RNA polymerase I is essential for driving the formation of 3D genome in early embryonic development in mouse, but not in human.

Background: Three-dimensional (3D) chromatin architecture undergoes dynamic reorganization during mammalian gametogenesis and early embryogenesis. While mouse studies have shown species-specific patterns as well as mechanisms underlying de novo organization, these remain poorly characterized in humans. Although RNA polymerases II and III have been shown to regulate chromatin structure, the potential role of RNA polymerase I (Pol I), which drives ribosomal RNA production, in shaping 3D genome organization during these developmental transitions has not been investigated.

Methods: We employed a modified low-input in situ Hi-C approach to systematically compare 3D genome architecture dynamics from gametogenesis through early embryogenesis in human and mouse. Complementary Smart-seq2 for low-input transcriptomics, CUT&Tag for Pol I profiling, and Pol I functional inhibition assays were performed to elucidate the mechanisms governing chromatin organization.

Results: Our study revealed an extensive reorganization of the 3D genome from human oogenesis to early embryogenesis, displaying significant differences with the mouse, including dramatically attenuated topologically associating domains (TADs) at germinal vesicle (GV) stage oocytes. The 3D genome reconstruction timing is a fundamental difference between species. In human, reconstruction initiates at the 4-cell stage embryo in human, while in mouse, it commences at the 2-cell stage embryo. We discovered that Pol I is crucial for establishing the chromatin structures during mouse embryogenesis, but not in human embryos. Intriguingly, the absence of Pol I transcription weakens TAD structure in mouse female germline stem cells, whereas it fortifies it in human counterparts.

Conclusions: These observed interspecies distinctions in chromatin organization dynamics provide novel insights into the evolutionary divergence of chromatin architecture regulation during early mammalian development. Our findings provide mechanistic insights into species-specific chromatin organization during germ cell and embryonic development and have potential implications for fertility preservation and birth defect prevention.

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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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