ubH2A对异染色质结构与功能的调控机制研究

作为表观遗传调控的重要平台，染色质结构的动态性和可塑性在基因转录调控中发挥重要作用。ubH2A(H2AK119ub1)由PRC1复合物催化产生，是兼性异染色质的标志之一，在异染色质结构和功能的调控中扮演了重要角色。我们的前期工作发现，ubH2A可以通过阻碍DNA从组蛋白八聚体上的剥离来增强单个核小体的机械稳定性。但是，在染色质层面上它是如何调控异染色质的结构和功能还尚不明确。本项目旨在以ubH2A为中心，利用单分子磁镊技术、组学方法与传统生化相结合的研究手段，探讨结构蛋白H1、组蛋白修饰酶PRC1以及转录因子FACT如何与ubH2A相互作用共同调控异染色质结构的分子机制，从而为深入理解ubH2A在转录调控中的功能提供理论依据。

As an important platform for epigenetic regulation, the dynamics and plasticity of chromatin structure play an important role in gene transcription regulation. ubH2A(H2AK119ub1) is catalyzed by the PRC1 complex and is one of the hallmarks of facultative heterochromatin. It plays an important role in the regulation of the structure and function of heterochromatin. Our previous work found that ubH2A can enhance the mechanical stability of the nucleosome by blocking the peeling of DNA from the histone octamer. However, how it regulates the structure and function of heterochromatin at the chromatin level is still unclear. This project aims to focus on ubH2A, using single-molecule magnetic tweezers technology, genomics methods and traditional biochemical research methods to explore how structural protein H1, histone modifying enzyme PRC1, and transcription factor FACT interact with ubH2A to regulate the structure of heterochromatin. The molecular mechanism of chromatin structure provides a theoretical basis for in-depth understanding of the function of ubH2A in transcriptional regulation.