Narrow H3K4me2 is required for chicken PGC formation

窄H3K4me2是鸡PGC形成所必需的

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作者:Chen Zhang, Qisheng Zuo, Man Wang, Hao Chen, Nana He, Jing Jin, Tingting Li, Jingyi Jiang, Xia Yuan, Jiancheng Li, Xiang Shi, Ming Zhang, Hao Bai, Yang Zhang, Qi Xu, Hengmi Cui, Guobin Chang, Jiuzhou Song, Hongyan Sun, Yani Zhang, Guohong Chen, Bichun Li

Abstract

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.

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