Differential regulation of mesoscale chromosome conformations in osteoblasts and osteosarcoma

IF 10.1 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Madhoolika Bisht, Yu-Chieh Chung, Siou-Luan He, Sydney Willey, Benjamin D. Sunkel, Meng Wang, Benjamin Z. Stanton, Li-Chun Tu
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Abstract

Chromosome conformation within the nucleus is essential for genome function. These have primarily been studied at the scale of loops and compartments, or at lower spatial resolution using traditional in situ hybridization in chemically fixed samples. However, the mesoscale organization of single chromosomes in vivo, shaped by the interplay between chromatin architectural proteins and histone modifications, remains partially understood. In this study, we interrogated the mesoscale conformations of interphase chromosomes in live human osteoblasts and transformed osteosarcoma cells, focusing on chromosome 19. Chromosome conformations were quantified by the aspect ratio of the principal axes of gyration tensors. In osteoblasts, approximately 81% of chromosome 19 are observed to consist of regions characterized by highly extended organizations, with aspect ratios approximately four times greater than those of spheres. In contrast, in osteosarcoma cells, the chromosome displays an extensively collapsed conformation, with aspect ratios more closely approximately that of a sphere. In both cell types, the chromosome’s conformation is bimodal and the balance between these two modes differs very significantly between the two cell types. While the mesoscopic conformation is considerably stable, it is superimposed on dynamic, smaller scale regions. Additional results reveal that this significant conformational shift is independent of the cell cycle but co-regulated by CTCF, cohesion, and H3K27 modifications. Our findings provide new insights into the coordinated complex regulatory mechanisms governing mesoscale chromosome organization in normal and transformed osteogenic tissues.
成骨细胞和骨肉瘤中尺度染色体构象的差异调控
细胞核内的染色体构象对基因组的功能至关重要。这些主要是在环和隔室的尺度上进行研究,或者在化学固定样品中使用传统的原位杂交在较低的空间分辨率下进行研究。然而,体内单染色体的中尺度组织,由染色质结构蛋白和组蛋白修饰之间的相互作用形成,仍然部分被理解。在这项研究中,我们研究了活的人成骨细胞和转化骨肉瘤细胞间期染色体的中尺度构象,重点研究了19号染色体。染色体构象通过旋转张量主轴的纵横比来量化。在成骨细胞中,约81%的19号染色体由高度延伸的组织组成,其纵横比约为球体的四倍。相反,在骨肉瘤细胞中,染色体显示出广泛折叠的构象,其长宽比更接近于球体。在这两种细胞类型中,染色体的构象都是双峰的,这两种模式之间的平衡在两种细胞类型之间差别很大。虽然介观构象相当稳定,但它是叠加在动态的、较小尺度的区域上的。其他结果表明,这种显著的构象变化与细胞周期无关,但受CTCF、内聚和H3K27修饰的共同调节。我们的发现为正常和转化成骨组织中尺度染色体组织的协调复杂调控机制提供了新的见解。
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来源期刊
Genome Biology
Genome Biology Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
21.00
自引率
3.30%
发文量
241
审稿时长
2 months
期刊介绍: Genome Biology stands as a premier platform for exceptional research across all domains of biology and biomedicine, explored through a genomic and post-genomic lens. With an impressive impact factor of 12.3 (2022),* the journal secures its position as the 3rd-ranked research journal in the Genetics and Heredity category and the 2nd-ranked research journal in the Biotechnology and Applied Microbiology category by Thomson Reuters. Notably, Genome Biology holds the distinction of being the highest-ranked open-access journal in this category. Our dedicated team of highly trained in-house Editors collaborates closely with our esteemed Editorial Board of international experts, ensuring the journal remains on the forefront of scientific advances and community standards. Regular engagement with researchers at conferences and institute visits underscores our commitment to staying abreast of the latest developments in the field.
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