PGC7通过抑制YY1与PRC2的相互作用来调节H3K27me3的修饰
Weijie Hao1, Chenyang Huang1, Defu Liu1
1College of Veterinary Medicine, Northwest A&F University, Yangling, China.
American journal of physiology. Cell physiology
|June 12, 2023
概括
原始生殖细胞7 (PGC7) 通过控制DNA甲基化来调节早期胚胎发育. PGC7影响增强器的胃类同源2 (EZH2) 活动和局部化,影响素H3氨酸27三甲基化 (H3K27me3) 水平和囊基因激活.
科学领域:
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 原始生殖细胞7 (PGC7),也称为Dppa3或Stella,对于DNA甲基化重编程在印记位置至关重要.
- PGC7与阴阳1 (YY1) 相互作用,这是招募含有聚合物抑制复合物2 (PRC2) 的凝肠同类2 (EZH2) 增强剂的必要蛋白质.
- 囊胞中PGC7缺乏导致细胞循环在双细胞阶段停止,并增加了素H3氨酸27三甲基化 (H3K27me3).
研究的目的:
- 阐明PGC7调节H3K27me3水平并影响果基因组激活的机制.
- 在早期胚胎发育的背景下,研究PGC7,YY1,EZH2和PRC2之间的相互作用.
主要方法:
- 同免疫沉试验用于研究蛋白质与蛋白质相互作用.
- 西方斑点测试用于评估蛋白质含量和酸化.
- 免疫光显微镜以确定蛋白质定位.
- 分析H3K27me3水平和在卵巢和早期胚胎中的基因表达.
主要成果:
- PGC7削弱了YY1和PRC2之间的相互作用,而不影响PRC2核心子单元组件.
- PGC7促进了AKT介导的EZH2在21级蛋白中的酸化,抑制了EZH2的活性,并导致EZH2与YY1.1分离.
- 无论是PGC7缺乏还是AKT抑制 (MK2206),都会增加胚胎细胞中的核EZH2和H3K27me3水平,抑制胚胎基因激活并影响胚胎早期发育.
结论:
- PGC7通过调节PRC2招募,EZH2活动和亚细胞局部化来调节H3K27me3水平.
- 这些PGC7的调节作用对于成功的胚胎基因组激活和正常的早期胚胎发育至关重要.
- 这些发现揭示了一种涉及PGC7在早期胚胎发生过程中的表观遗传调节中的新机制.
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