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

Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells.
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核外周染色质-核纤层蛋白 B1 相互作用是人类细胞染色质结构和动力学的整体完整性所必需的

DOI:
10.1007/s13238-020-00794-8
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发表时间:
2022-04
期刊:
影响因子:
21.1
通讯作者:
Sun Y
Sun Y
中科院分区:
生物学1区
文献类型:
--
作者:
Chang L;Li M;Shao S;Li C;Ai S;Xue B;Hou Y;Zhang Y;Li R;Fan X;He A;Li C;Sun Y

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真核生物的基因组折叠成更高的顺序构象,伴随着协调基因组功能的约束动力学。然而,这些分层组织的三维(3D)染色质结构和动力学的分子机制仍然知之甚少。通过结合成像和测序,我们研究了核纤层蛋白B1在染色质结构和动力学中的作用。我们发现,核纤层蛋白B1耗竭导致脱离核纤层相关结构域(LAD)从核周边伴随着全球染色质重新分布和解压缩。因此,染色体间以及隔室间的相互作用增加,但拓扑关联结构域(TADs)的结构不受影响。使用活细胞基因组位点跟踪,我们进一步证明了核纤层蛋白B1的耗竭导致染色质动力学增加,这是由于染色质分解和向核质的重新分布。总之,我们的数据表明,核纤层蛋白B1和染色质在核周围的相互作用,促进LAD的维护,染色质压实,基因组区室化到染色体领土和A/B区室和限制染色质动力学,支持其在染色质高阶结构和染色质动力学的关键作用。
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 inter-chromosomal 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 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.
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