Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Physiol. 2021 Feb;236(2):1391-1400. doi: 10.1002/jcp.29945. Epub 2020 Aug 4.
The development of primordial germ cells (PGCs) undergoes epigenetic modifications. The study of histone methylation in regulating PGCs is beneficial to understand the development and differentiation mechanism of germ stem cells. Notably, it provides a theoretical basis for directed induction and mass acquisition in vitro. However, little is known about the regulation of PGC formation by histone methylation. Here, we found the high enrichment of H3K4me2 in the blastoderm, genital ridges, and testis. Chromatin immunoprecipitation sequencing was performed and the results revealed that genomic H3K4me2 is dynamic in embryonic stem cells, PGCs, and spermatogonial stem cells. This trend was consistent with the H3K4me2 enrichment in the gene promoter region. Additionally, narrow region triggered PGC-related genes (Bmp4, Wnt5a, and Tcf7l2) and signaling pathways (Wnt and transforming growth factor-β). After knocking down histone methylase Mll2 in vitro and vivo, the level of H3K4me2 decreased, inhibiting Cvh and Blimp1 expression, then repressing the formation of PGCs. Taken together, our study revealed the whole genome map of H3K4me2 in the formation of PGCs, contributing to improve the epigenetic study in PGC formation and providing materials for bird gene editing and rescue of endangered birds.
原始生殖细胞 (PGC) 的发育经历了表观遗传修饰。研究组蛋白甲基化在调控 PGC 中的作用，有利于理解生殖干细胞的发育和分化机制。值得注意的是，它为体外定向诱导和大量获取提供了理论基础。然而，人们对组蛋白甲基化调控 PGC 形成的机制知之甚少。在这里，我们发现 H3K4me2 在囊胚、生殖嵴和睾丸中高度富集。进行染色质免疫沉淀测序，结果表明胚胎干细胞、PGC 和精原干细胞中的基因组 H3K4me2 是动态的。这一趋势与基因启动子区域 H3K4me2 的富集一致。此外，窄区域触发与 PGC 相关的基因（Bmp4、Wnt5a 和 Tcf7l2）和信号通路（Wnt 和转化生长因子-β）。在体外和体内敲低组蛋白甲基转移酶 Mll2 后，H3K4me2 水平降低，抑制 Cvh 和 Blimp1 的表达，从而抑制 PGC 的形成。综上所述，本研究揭示了 PGC 形成过程中 H3K4me2 的全基因组图谱，有助于提高 PGC 形成中的表观遗传学研究，并为鸟类基因编辑和拯救濒危鸟类提供材料。
