Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamic
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Protein & Cell
RESEARCH ARTICLE
Lei Chang1,6 , Mengfan Li2,3 , Shipeng Shao1 , Chen Li4, Shanshan Ai4, Boxin Xue1, Yingping Hou2,3, Yiwen Zhang1, Ruifeng Li2,3, Xiaoying Fan6, Aibin He2,4, Cheng Li3,5& , Yujie Sun1& 1
State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China 2 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China 3 Center for Bioinformatics, School of Life Sciences, Peking University, Beijing 100871, China 4 Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China 5 Center for Statistical Science, Peking University, Beijing 100871, China 6 Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510530, China & Correspondence: [email protected] (C. Li), [email protected] (Y. Sun) Received June 29, 2020 Accepted September 7, 2020
ABSTRACT The eukaryotic genome is folded into higher-order conformation 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 combining 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 redistribution and decompaction. Consequently, the interchromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion
Lei Chang, Mengfan Li and Shipeng Shao contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13238-020-00794-8) contains supplementary material, which is available to authorized users.
© The Author(s) 2020
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 compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
KEYWORDS lamin B1, 3D genome, Hi-C, chromatin dynamics, chromosome territories, A/B compartments, livecell imaging, super-resolution imaging INTRODUCTION Chromatin in the interphase nucleus of eukaryotic cells is highly compartmentalized and structured. Owing to technological breakthroughs in imaging (Boettiger et al., 2016; Wang et al., 2016; Bintu et al., 2018) and sequencing (Dekker et al., 2002; Dosti
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