Topological isolation of developmental regulators in human

发布者:文明办发布时间:2021-03-16浏览次数:274


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.