多梳抑制复合物介导表观遗传记忆的分子机制及其生物学功能

PRC1是一类重要的多梳抑制复合物，它通过压缩染色质和单泛素化H2A介导了兼性异染色质的形成。在前期工作中，我们发现非常规PRC1以正反馈方式促进了H2AK119ub1向邻近核小体的蔓延，并利用TetR/TetO靶向系统证明该机制对H2AK119ub1在异染色质区域的继承至关重要。然而，H2AK119ub1是如何遗传的以及它如何调控染色质结构和基因表达的目前仍不清楚。本项目中，我们将利用定量质谱和ChIP-seq等技术系统研究DNA复制时H2AK119ub1传递的机制及其在新生染色质上恢复的时空规律，并探讨正反馈机制、组蛋白H1以及组蛋白分子伴侣等因子在该过程中发挥的调控作用。同时，我们将在染色质层面深入研究H2AK119ub1调控基因差异性表达的分子机理。总之，该研究将为理解表观遗传现象提供理论依据。

PRC1 is an important polycomb repressive complex, which is pivotal for heterochromatin organization through chromatin compaction and H2AK119ub1. We previously found that non-canonical PRC1 promotes the propagation of H2AK119ub1 on neighboring nucleosomes through a positive-feedback model, and we showed that this mechanism is required for the inheritance of H2AK119ub1 at heterochromatin regions in TetR/TetO targeting system. However，it remains unclear how H2AK119ub1 is inherited and what the function of H2AK119ub1 on chromatin structure and gene regulation. In this study, we sought to elucidate the transmission and spatiotemporal restoration of H2AK119ub1 at newly replicated chromatin during DNA replication using SILAC-MS and ChIP-seq analysis. In addition, we will investigate the regulatory roles of positive feedback model, histone H1 and histone chaperone in this process. Furthermore, we will investigate the regulatory mechanisms of H2AK119ub1 on differential gene expression at chromatin level. In sum, our study will provide theoretical foundation for epigenetic inheritance.