Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

• 作者: Lei Chang Mengfan Li Shipeng Shao Chen Li Shanshan Ai Boxin Xue Yingping Hou Yiwen Zhang Ruifeng Li Xiaoying Fan Aibin He Cheng Li Yujie Sun
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2022,（4）
• 所属期刊栏目: RESEARCH ARTICLES
• 页码范围: 258-280
• 页数: 23页
• 语种: 英文

摘要

The eukaryotic genome is folded into higher-order con-formation accompanied with constrained dynamics for coordinated genome functions.However,the molecular machinery underlying these hierarchically organized three-dimensional(3D)chromatin architecture and dynamics remains poorly understood.Here by combin-ing imaging and sequencing,we studied the role of lamin B1 in chromatin architecture and dynamics.We found that lamin B1 depletion leads to detachment of lamina-associated domains(LADs)from the nuclear periphery accompanied with global chromatin redistri-bution and decompaction.Consequently,the inter-chromosomal as well as inter-compartment interactions are increased,but the structure of topologically asso-ciating domains(TADs)is not affected.Using live-cell genomic loci tracking,we further proved that depletion of lamin B1 leads to increased chromatin dynamics,owing to chromatin decompaction and redistribution toward nucleoplasm.Taken together,our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance,chromatin com-paction,genomic compartmentalization into chromo-some territories and A/B compartments and confine chromatin dynamics,supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.