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The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes

机译:人和小鼠基因组的详细3D多环聚集/玫瑰红染色质结构和功能动态组织

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Background The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function—the storage, expression, and replication of genetic information—is still one of the central issues in biology. Here, we describe the much debated 3D architecture of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture ( T2C ), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence. Results The genome is compacted into a chromatin quasi-fibre with ~5?±?1?nucleosomes/11?nm, folded into stable ~30–100?kbp loops forming stable loop aggregates/rosettes connected by similar?sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence show very similar fine-structured multi-scaling behaviour confirming their co-evolution and the above. Conclusions This architecture, its dynamics, and accessibility, balance stability and flexibility ensuring genome integrity and variation enabling gene expression/regulation by self-organization of (in)active units already in proximity. Our results agree with the heuristics of the field and allow “architectural sequencing” at a genome mechanics level to understand the inseparable systems genomic properties.
机译:背景技术基因组的动态三维染色质结构及其与功能的共同进化联系(遗传信息的存储,表达和复制)仍然是生物学的中心问题之一。在这里,我们通过结合选择性高通量高分辨率染色体相互作用捕获(T2C),聚合物模拟和分子比例分析的新颖方法,描述了从核小体到兆碱基对水平的人类和小鼠基因组备受争议的3D结构。 3D结构和DNA序列。结果基因组被压缩成染色质准纤维,具有〜5?±?1?核小体/ 11?nm,折叠成稳定的〜30–100?kbp环,形成由相似大小的接头连接的稳定的环聚集体/红斑。在单元格类型和功能状态之间可以看到架构上的微小但重要的变化。该结构和DNA序列显示出非常相似的精细结构的多尺度行为,证实了它们的共同进化及以上。结论该架构,其动态性和可及性,平衡稳定性和灵活性确保了基因组的完整性和变异性,通过已经存在的(非)活性单位的自组织实现基因表达/调控。我们的结果与该领域的启发法相吻合,并允许在基因组力学水平上进行“建筑测序”以了解不可分割的系统的基因组特性。

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