Knoch Tobias A, Wachsmuth Malte, Kepper Nick, Lesnussa Michael, Abuseiris Anis, Ali Imam A M, Kolovos Petros, Zuin Jessica, Kockx Christel E M, Brouwer Rutger W W, van de Werken Harmen J G, van IJcken Wilfred F J, Wendt Kerstin S, Grosveld Frank G
Biophysical Genomics, Department of Cell Biology and Genetics, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstr. 1, 69117, Heidelberg, Germany.
Epigenetics Chromatin. 2016 Dec 24;9:58. doi: 10.1186/s13072-016-0089-x. eCollection 2016.
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 (), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence.
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.
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.
基因组的动态三维染色质结构及其与功能(遗传信息的存储、表达和复制)的共同进化联系仍然是生物学的核心问题之一。在此,我们通过一种新颖的方法,将选择性高通量高分辨率染色体相互作用捕获、聚合物模拟以及三维结构和DNA序列的标度分析相结合,从核小体到兆碱基对水平描述了备受争议的人类和小鼠基因组三维结构。
基因组被压缩成一种染色质准纤维,每11纳米约有5±1个核小体,折叠成稳定的约30 - 100千碱基对的环,形成由类似大小的连接体连接的稳定环聚集体/玫瑰花结。在细胞类型和功能状态之间可以看到结构上微小但显著的差异。结构和DNA序列显示出非常相似的精细结构多标度行为,证实了它们的共同进化以及上述情况。
这种结构、其动态性和可及性,平衡了稳定性和灵活性,确保了基因组的完整性和变异性,通过已经相邻的(非)活性单元的自组织实现基因表达/调控。我们的结果与该领域的启发式观点一致,并允许在基因组力学水平进行“结构测序”,以理解不可分割的系统基因组特性。