人类产前生殖系发育过程中组蛋白修饰的重编程。
Resetting histone modifications during human prenatal germline development.
作者信息
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
机构信息
Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
出版信息
Cell Discov. 2023 Feb 3;9(1):14. doi: 10.1038/s41421-023-00519-1.
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.
组蛋白修饰在调控基因表达中发挥着关键作用，并且在早期胚胎发育过程中呈现动态变化。然而，它们在人类产前生殖系发育过程中是如何重新编程的，目前尚未阐明。在此，我们首次通过进行ULI-NChIP-seq绘制了妊娠第8至23周人类原始生殖细胞（hPGCs）中三种关键组蛋白修饰的全基因组图谱。值得注意的是，H3K4me3呈现出典型的启动子富集模式，尽管富集程度相对较低，并且在整体低甲基化的hPGCs中与基因表达呈正相关。此外，H3K27me3的富集程度非常低，但不仅在动态调控特定的双价启动子方面发挥重要作用，而且在阻碍女性hPGCs中X染色体的完全重新激活方面也发挥重要作用。鉴于全局DNA去甲基化和H3K4me3信号的激活作用，抑制性的H3K9me3和H3K27me3标记共同负责hPGCs中抗去甲基化区域的矛盾调控。总体而言，我们的结果提供了hPGC发育过程中三种核心组蛋白修饰的独特路线图，这有助于阐明在极度低甲基化的DNA环境中生殖细胞重编程的结构。
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