真核细胞基因组DNA与组蛋白组装形成染色质。所有有关DNA的生命活动都在染色质这个结构平台上进行。在高等生物发育过程中，细胞通过调控染色质结构，选择性进行基因沉默与激活，控制细胞自我维持或定向分化。研究染色质结构建立及其动态调控的分子机制对于理解这些过程具有非常重要的生物学意义。虽然目前染色质结构单元核小体的结构已被解析，但是核小体结构的建立、重塑及动态调控机制仍然并不清楚。而且对于染色质二级结构30nm染色质纤维的结构及动态调控的研究还非常有限。本项目基于染色质体外重建系统，应用生物物理和生物化学技术，包括分析超速离心、高精度冷冻电镜、单分子光学和力学等，结合细胞内染色质结构功能研究，系统研究组蛋白H2A化学修饰及变体对染色质结构动态调控的分子机制。通过本项目研究，我们将建立一套研究染色质分子结构及其动态调控的技术平台，为探讨其它重要表观遗传现象对染色质结构和功能调控的分子机制奠定基础。

In eukaryotes, genomic DNA is highly packaged into chromatin by histones to fit inside the nucleus. Dynamics of the chromatin structure plays a critical role in all DNA-related biological processes including transcriptional regulation, DNA replication and DNA repair. The transcriptional signatures of cells are highly regulated by the dynamic organization of chromatin structures, which also play particular important roles in cell fate determination/maintenance during embryonic stem (ES) cell programming and reprogramming processes. Thus, to investigate the establishment of chromatin structures and their dynamic regulation is a central question in the field of cell biology and epigenetics. Although the crystal X-ray studies have defined the structure of nucleosomes, the basic units of chromatin, the establishment and remodelling of the structure and its epigenetic regulations in nucleosome level are still remained to be addressed. In addition, how the primary structure of chromatin, a beads-on-a-string nucleosomal fiber compacted into a condensed 30nm chromatin fiber, the secondary structure of chromatin and how this process is regulated by different epigenetic mechanisms are still obscure. In this project, based on an in-vitro chromatin reconstitution system we have successfully developed, we are going to extensively investigate the molecular mechanism on the establishment of chromatin structure (including the mono-nucleosome and 30nm chromatin fibers) and its epigenetic regulation (focusing on the histone variant H2A.Z and H2A ubiquitination) using molecular biology, biophysics and biochemistry techniques, including the analytical ultracentrifugation, EM/cryo-EM and single-molecular FRET imaging and magnetic tweezers. Through this study, we will try to establish a new research platform to identify the molecular mechanism of the formation and dynamics of chromatin structures and its functions in transcriptional regulation.