BMP4 通过改变 H3K4me2 激活 Wnt-Wnt 通路，促进原始生殖细胞的形成。
BMP4 activates the Wnt---Wnt pathway to promote primordial germ cell formation via altering H3K4me2.
机构信息
Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, Jiangsu 225009, China.
出版信息
J Cell Sci. 2021 Feb 1;134(3):jcs249375. doi: 10.1242/jcs.249375.
The unique developmental characteristics of chicken primordial germ cells (PGCs) enable them to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits their application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the mechanism underlying chicken PGC formation has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of by inducing β-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the promoter and enhancing H3K4me2 methylation in this region. promotes PGC formation by inhibiting maturation to initiate expression. Interestingly, expression of helped sustain expression by preventing LSD1 binding to the promoter. We thus elucidated a positive feedback pathway involving Wnt---Wnt that ensures PGC formation. In summary, our data provide new insight into the development of PGCs in chickens
鸡原始生殖细胞（PGCs）独特的发育特点使其能够用于濒危鸟类物种的恢复、基因编辑和转基因鸟类的产生，但 PGCs 的数量有限极大地限制了其应用。研究表明，哺乳动物 PGC 的形成是由 BMP4 信号诱导的，但鸡 PGC 形成的机制尚未确定。在这里，我们证实，通过 BMP4 激活的 Wnt 信号通过诱导 β-连环蛋白与 TCF7L2 竞争结合，使 LSD1 从 启动子解离，并增强该区域的 H3K4me2 甲基化，从而激活转录。通过抑制 成熟来启动 表达，从而促进 PGC 的形成。有趣的是， 的表达通过阻止 LSD1 结合到 启动子上来帮助维持 的表达。因此，我们阐明了一个涉及 Wnt---Wnt 的正反馈途径，该途径确保了 PGC 的形成。总之，我们的数据为鸡 PGC 的发育提供了新的见解。
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