有丝分裂期染色质书签的建立和调控机制研究

有丝分裂期间，染色质固缩成染色体，大量染色质开放位点丢失，仅依赖少量染色质书签开放位点，保证细胞在退出有丝分裂后能快速重建细胞身份。然而目前对染色质书签开放位点，仍缺乏系统性、连续性的鉴定及调控机制研究。因此，本项目将利用染色质可及性测序技术（ATAC-seq）和单细胞染色质可及性技术（scATAC-seq），鉴定不同细胞系在有丝分裂期时期的染色质开放位点动态变化图谱，从而描绘有丝分裂期书签的建立和维持机制。通过开发生物信息学分析方法，比较不同细胞系的染色质书签差异，研究有丝分裂期书签对细胞特性维持、和转录激活的的调控机制。进一步，通过染色质开放位点鉴定相关转录调控因子，描绘细胞特性重建过程中的转录因子调控网络，并筛选关键调控因子。综上，我们的研究提供了首个系统性、连续性的有丝分裂期染色质开放位点图谱，并揭示了染色质书签的建立和基于转录因子的调控机制。

Chromatin condenses into chromosomes during mitosis, combining with lost of a large number of chromatin open sites. Only a small number of chromatin bookmark open sites are kept open to ensure that cells can quickly re-establish lineage fidelity after mitosis exit. However, systematic and dynamic identification and regulatory mechanism study of chromatin bookmarking open sites are still poorly understodd. Therefore, in order to describe the establishment and maintenance mechanism of mitotic bookmarks, our project will use chromatin accessibility sequencing technology (ATAC-seq) and single-cell chromatin accessibility technology (scATAC-seq) to identify the dynamic changes of chromatin open sites in different cell lines during mitosis.. Through the development of bioinformatics analysis methods, the differences in chromatin bookmarks of different cell lines are compared, and the regulatory mechanism of mitotic bookmarks on the maintenance of cell characteristics and transcription activation is studied. Furthermore, the relevant transcriptional regulatory factors are identified through the open sites of chromatin, the transcription factor regulatory network in the process of rebuilding cell characteristics is depicted, and key regulatory factors are screened. In summary, our research is the first to provide a systematic and continuous map of chromatin open sites during mitosis, and reveal the establishment of chromatin bookmarks and the regulatory mechanism based on transcription factors.