真核基因组被折叠成高阶构象,并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。在这里,通过结合成像和测序,我们研究了LaminB1在染色质结构和动力学中的作用。我们发现,层粘连蛋白B1耗竭会导致层相关结构域(LADs)从核外围脱离,并伴有整体染色质重新分布和分解。因此,染色体间以及隔室间的相互作用增加,但是拓扑关联域(TAD)的结构不受影响。使用活细胞基因组基因座跟踪,我们进一步证明了laminB1的消耗导致染色质动力学增加,由于染色质分解和向核质的重新分布。一起来看,我们的数据表明,在核外围的层粘连蛋白B1和染色质相互作用促进LAD的维持,染色质压实,基因组划分为染色体区域和A/B区室,并限制染色质动力学,支持它们在染色质高阶结构和染色质动力学中的关键作用。
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.