Lee Sun-Min, Surani M Azim
Department of Physics, Konkuk University, Seoul, Korea.
Wellcome Trust/Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Cambridge, UK.
Exp Mol Med. 2024 Dec;56(12):2578-2587. doi: 10.1038/s12276-024-01359-z. Epub 2024 Dec 13.
Primordial germ cells (PGCs) are the precursors of sperm and eggs. They undergo genome-wide epigenetic reprogramming to erase epigenetic memory and reset the genomic potential for totipotency. Global DNA methylation erasure is a crucial part of epigenetic resetting when DNA methylation levels decrease across the genome to <5%. However, certain localized regions exhibit slower demethylation or resistance to reprogramming. Since DNA methylation plays a crucial role in transcriptional regulation, this depletion in PGCs requires mechanisms independent of DNA methylation to regulate transcriptional control during PGC reprogramming. Histone modifications are predicted to compensate for the loss of DNA methylation in gene regulation. Different histone modifications exhibit distinct patterns in PGCs undergoing epigenetic programming at the genomic level during PGC development in conjunction with changes in DNA methylation. Together, they contribute to PGC-specific genomic regulation. Recent findings related to these processes provide a comprehensive overview of germline epigenetic reprogramming and its importance in mouse and human PGC development. Additionally, we evaluated the extent to which in vitro culture techniques have replicated the development processes of human PGCs.
原始生殖细胞(PGCs)是精子和卵子的前体。它们经历全基因组表观遗传重编程,以消除表观遗传记忆并重置基因组的全能性潜力。当全基因组DNA甲基化水平降至<5%时,全基因组DNA甲基化擦除是表观遗传重置的关键部分。然而,某些局部区域表现出较慢的去甲基化或对重编程的抗性。由于DNA甲基化在转录调控中起关键作用,PGCs中的这种耗竭需要独立于DNA甲基化的机制来在PGC重编程过程中调节转录控制。预计组蛋白修饰可补偿基因调控中DNA甲基化的缺失。在PGC发育过程中,不同的组蛋白修饰在基因组水平上经历表观遗传编程的PGCs中表现出不同的模式,同时伴随着DNA甲基化的变化。它们共同促成了PGC特异性的基因组调控。与这些过程相关的最新发现全面概述了生殖系表观遗传重编程及其在小鼠和人类PGC发育中的重要性。此外,我们评估了体外培养技术在多大程度上复制了人类PGC的发育过程。