人原始生殖细胞中的关键组蛋白修饰动态调控机制研究

生殖细胞为同一物种内所有世代之间提供了联系的纽带，它不仅具备产生新的生物个体的能力，还通过其独特的方式将遗传信息从一代传递至下一代。在哺乳动物中，作为生殖细胞的来源，原始生殖细胞在胚胎发育的早期就已形成，并经历了广泛和彻底的表观遗传重编程。我们前期的研究已初步发现H3K4me3和H3K27me3修饰对人原始生殖细胞转录的协同调控，但是这些关键组蛋白修饰的具体变化模式和相互关联仍有待进一步被阐述。本研究将充分利用课题组已建立的微量组学技术及相关分析方法，以人胚胎发育中的原始生殖细胞为研究对象，结合hPGCLC体外分化系统，系统揭示人PGC发育中关键组蛋白修饰（H3K4me3、H3K27me3和H3K9me3）的建立和动态变化模式、相互关联及其与DNA甲基化协同调控PGC命运的机制。

The germ cells provide an enduring link between all generations of a species. They are unique not only in the ability to give rise to a new organism, but also in transmitting the genetic and epigenetic information from one generation to the next. In mammals, primordial germ cells (PGCs), the founder cells of the germ line, are specified during early embryonic development and undergo extensive and thorough epigenetic reprogramming. Our preliminary data has shown that H3K4me3 and H3K27me3 coordinate to regulate the transcription of hPGCs. However, the detailed dynamic changes and interactions of these key histone modifications in the development process remain unclear. In the present study, we will make full use of our small-scale ChIP–seq technology and advanced bioinformatic method to deeply investigate the genome-wide profiles as well as the interactions of three histone modifications – H3K4me3, H3K27me3 and H3K9me3 during human PGC specification. In addition, by applying the hPGCLC in vitro induction system, we will further discuss the interactome of these histone modifications and DNA methylation in regulating hPGC development.