uH2A在染色质高级结构及基因表达调控中的生物学功能研究

H2AK119位泛素化（uH2A)是一种重要的组蛋白翻译后修饰，它由PRC1(polycomb repressor complex 1)的核心亚基Ring1B催化形成，在PRC1调控发育基因表达方面发挥重要的作用。基因敲除实验证明，PRC1的核心催化亚基Ring1B是胚胎发育必须的，但是PRC1如何利用uH2A调控发育基因的机制仍不清楚。本项目将在核小体稳定性、染色质折叠与去折叠以及H1介导的30nm染色质形成等方面研究uH2A对染色质高级结构的影响，同时我们将利用小鼠胚胎干细胞神经定向分化模型，研究uH2A在神经分化过程中调控染色质高级结构变化的规律，以及uH2A与PRC1和H1协同调控分化基因表达的机理。通过本项目的研究，我们将从分子水平上揭示uH2A影响染色质高级结构的机理，阐明其在基因表达调控中的作用，从而理解uH2A在胚胎发育过程中的生物学功能及其分子机理。

uH2A is an important histone post-translational modification, which plays pivotal roles in the regulation of developmental genes by PRC1. As the core subunit of PRC1, Ring1B is the main ubiquitin ligase E3 for uH2A and indispensable for embryonic development. Confusingly, the role of uH2A in PRC1 regulation is still unclear. In this study, we will mainly examine the effects of uH2A in regulating higher-ordered chromatin structure at several levels, including: nucleosome stability, chromatin folding and 30nm chromatin formation mediated by H1 and so on. Meanwhile, using the neuronal differentiation model established in mouse embryonic stem cells(ESC) , we will explore the roles of uH2A in regulating higher-ordered chromatin structure and the synergetic regulatory roles of uH2A H1 and PRC1 in regulating differential genes in vivo. Through this study, we are going to illuminate the molecular mechanisms of uH2A in higher-ordered chromatin and gene regulation, to further understanding the biological functions and molecular mechanisms of uH2A in development.