主讲人:吴华君 北京大学研究员
时间:2021年3月19日10:00
地点:三号楼332会议厅
举办单位:数理学院
内容介绍:Precise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSC) that allowed us to identify CTCF loop domains with highly conserved boundary CTCF sites and a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings demonstrate the importance of gene insulation through chromosomal folding structures as a mechanism to ensure proper expression of many developmental regulators.