Resetting histone modifications during human prenatal germline development.
Resetting histone modifications during human prenatal germline development.
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DOI：
10.1038/s41421-023-00519-1
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发表时间：
2023-02-03
期刊：
影响因子：
33.5
通讯作者：
Chen, Jiayu
中科院分区：
文献类型：
--
作者：
Gao, Rui;Zeng, Shiyang;Yang, Dongxu;Li, Xiaocui;Liu, Wenqiang;Gao, Yawei;Bai, Dandan;Zhang, Linfeng;Chen, Chuan;Kang, Yunzhe;Wang, Beiying;Hong, Wei;Wang, Mingzhu;Yin, Jiqing;Wang, Hong;Deng, Qiaolin;Gao, Shaorong;Zhang, Yong;Chen, Jiayu
组蛋白修饰在调控基因表达中起着关键作用，并在早期胚胎发育过程中呈现动态变化。然而，它们如何在人类产前生殖细胞发育过程中重新编程尚未阐明。在这里，我们通过执行ULI-NChIP-seq首次绘制了人类原始生殖细胞（hPGCs）中三个关键组蛋白修饰的全基因组图谱，从妊娠第8周到第23周。值得注意的是，H3 K4 me 3表现出典型的启动子富集模式，尽管富集相对较低，并且与整体低甲基化hPGC中的基因表达正相关。此外，H3 K27 me 3呈现非常低的富集，但在女性hPGC中不仅动态地控制特异性二价启动子而且阻碍完全X染色体再活化中起重要作用。考虑到全局DNA去甲基化和H3 K4 me 3信号的激活效应，抑制性H3 K9 me 3和H3 K27 me 3标记共同负责hPGC中去甲基化抗性区域的矛盾调节。总的来说，我们的研究结果提供了一个独特的路线图的三个核心组蛋白的修改在hPGC的发展，这有助于阐明生殖细胞重编程的架构在一个非常低甲基化的DNA环境。
Histone modifications play critical roles in regulating gene expression and present dynamic changes during early embryo development. However, how they are reprogrammed during human prenatal germline development has not yet been elucidated. Here, we map the genome-wide profiles of three key histone modifications in human primordial germ cells (hPGCs) from weeks 8 to 23 of gestation for the first time by performing ULI-NChIP-seq. Notably, H3K4me3 exhibits a canonical promoter-enriched pattern, though with relatively lower enrichment, and is positively correlated with gene expression in globally hypomethylated hPGCs. In addition, H3K27me3 presents very low enrichment but plays an important role in not only dynamically governing specific bivalent promoters but also impeding complete X chromosome reactivation in female hPGCs. Given the activation effects of both global DNA demethylation and H3K4me3 signals, repressive H3K9me3 and H3K27me3 marks are jointly responsible for the paradoxical regulation of demethylation-resistant regions in hPGCs. Collectively, our results provide a unique roadmap of three core histone modifications during hPGC development, which helps to elucidate the architecture of germ cell reprogramming in an extremely hypomethylated DNA environment.
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