Zhang Jingyu, Wang Siyuan, Watkins Simon C, Xing Jianhua
Department of Computational and Systems Biology, University of Pittsburgh; Pittsburgh, PA 15232, USA.
Department of Cell Biology, Yale School of Medicine; New Haven, CT 06510, USA.
bioRxiv. 2025 Feb 10:2025.02.10.637328. doi: 10.1101/2025.02.10.637328.
One fundamental yet open question is how eukaryotic chromosomes fold into segregated territories, a process essential for gene transcription and cell fate. Through analyzing Hi-C and chromatin-tracing DNA-FISH data, we identify long-range chromo skeleton loop structures that span over 100 Mb, extending beyond the reach of loop extrusion models. Spatial density analyses point to assembly formation independent of major nuclear structures. A subset of genomic loci serves as nucleation centers, driving loop clustering. These complexes are highly stable, as shown by live-cell imaging with sequence-specific fluorescent labeling, and biophysical model analyses reveal a multivalent binding mechanism. Our findings suggest a redundant, distributed cluster mechanism that ensures robustness across cell types and against mutations, guiding both chromosome compaction and the formation of smaller-scale chromosomal structures.
一个基本但尚未解决的问题是真核生物染色体如何折叠成隔离的区域，这一过程对基因转录和细胞命运至关重要。通过分析Hi-C和染色质追踪DNA-FISH数据，我们确定了跨越超过100 Mb的长程染色体骨架环结构，超出了环挤压模型的范围。空间密度分析表明组装形成独立于主要核结构。基因组位点的一个子集充当成核中心，驱动环聚集。如通过序列特异性荧光标记的活细胞成像所示，这些复合体高度稳定，生物物理模型分析揭示了一种多价结合机制。我们的研究结果提出了一种冗余的、分布式聚集机制，该机制确保跨细胞类型的稳健性并抵御突变，指导染色体压实和较小规模染色体结构的形成。
