在干细胞编程和重编程过程中，细胞主要通过表观遗传调控，包括DNA甲基化、组蛋白化学修饰及其变体等改变染色质高级结构，有选择地进行基因沉默和激活。染色质在细胞核内的高级结构主要包括30nm染色质纤维、染色质相互作用形成的拓扑功能域以及染色质纤维的核内定位等。目前对这些复杂染色质高级结构的结构特征和生物学功能的认识仍然十分有限。本项目将围绕染色质高级结构和细胞命运决定的表观遗传调控这一核心问题，从分子水平上研究30nm 染色质纤维超分子复合体的组装、精细结构和表观遗传调控机制、分析核内全基因组水平上的染色质高级结构功能域以及染色质纤维与核膜/核纤层相互作用的结构图谱及其在干细胞分化过程中的动态变化，为阐明细胞内各种染色质高级结构建立和维持的表观遗传调控机理及其在细胞命运决定中的生物学功能奠定基础。

During embryonic stem (ES) cell programming and reprogramming, the transcriptional signatures of ES cells are regulated by epigenetic mechanisms, including DNA methylation, histone modifications and histone variants, through changing the dynamics of higher-order chromatin structures. Higher-order chromatin organizations within the living nucleus appear to be organized in a hierarchical manner, including 30nm chromatin fibers, chromatin topological domains and chromatin nuclear positioning. However, it is still unclear how chromatin organizes into these complicated higher-order structures in nucleus. Thus, the study of epigenetic regulation and dynamics of higher-order chromatin organizations in the nucleus during stem cell programming and reprogramming is a central question in the field of stem cell biology and epigenetics. In this project, we are going to investigate the structural features and epigenetic regulation of 30nm chromatin fibers, the genome-wide chromatin higher-order organization in nucleus and their dynamic changes during ES cell programming and reprogramming in order to illuminate the molecular mechanisms of the establishment and epigenetic regulation of the hierarchical organization of chromatin in stem cells and their related biological function in cell fate determination.