Changes of chromosomal architecture before establishment of chromosome territories revealed by recurrence plot reconstruction

Changes of chromosomal architecture before establishment of chromosome territories revealed by recurrence plot reconstruction
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递归图重建揭示染色体区域建立前染色体结构的变化

DOI:
10.1101/2021.05.20.444916
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发表时间:
2022
期刊:
BioRxiv
影响因子:
--
通讯作者:
Yukiko Gotoh and Yoshito Hirata
Yukiko Gotoh and Yoshito Hirata
中科院分区:
--
文献类型:
--
作者:
Yuki Kitanishi;Hiroki Sugishita;Yukiko Gotoh and Yoshito Hirata

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近年来,与染色质构象捕获相关的方法如Hi-C,提高了我们对核结构和组织的理解。然而,由于DNA接触的有限信息,从单细胞Hi-C(scHi-C)数据重建单个细胞的核结构一直具有挑战性,这是由于从单细胞回收DNA的效率低。我们以前已经开发了一种算法,命名为“基于递归图的重建(RPR)方法”,用于重建三维(3D)基因组结构的单单倍体细胞和二倍体细胞的Hi-C数据。这种数学方法是基于递归图,一种用于可视化时间序列内的时间模式的非线性时间序列分析工具,并且即使从稀疏(低覆盖率)DNA接触信息也能够重建独特的3D染色体结构。在这里,我们应用RPR方法来分析已发表的scHi-C数据的二倍体细胞来源于早期的F1杂种胚胎。我们发现,父亲和母亲的染色体逐渐混合,从1细胞到64细胞阶段和离散的染色体领域(CT)主要建立在8细胞和64细胞阶段之间。我们还观察到从2细胞到8细胞阶段染色体呈Rabl样极化分布,但到64细胞阶段这种极化大部分消失。Rabl样构型的形成先于染色体形状的杆状延伸和它们的平行排列,暗示了Rabl样构型在建立CT之前在避免缠结和促进染色体的有效混合中的作用。我们还发现了一个细胞间的染色质构型的变异性。因此,scHi-C和RPR分析的组合可以表征早期胚胎发生期间不同发育阶段的个体细胞的不同3D染色质结构。
The chromatin conformation capture-related methods such as Hi-C have improved our understanding of nuclear architecture and organization in recent years. However, reconstruction of nuclear architecture of individual cells from single cell Hi-C (scHi-C) data has been challenging due to limited information of DNA contacts owing to the low efficiency of DNA recovery from a single cell. We have previously developed an algorithm named as “recurrence plot-based reconstruction (RPR) method” for reconstructing three dimensional (3D) genomic structure from Hi-C data of single haploid cells and diploid cells . This mathematical method is based on a recurrence plot, a tool of nonlinear time series analysis for visualizing temporal patterns within a time series,, and enables the reconstruction of a unique 3D chromosome architecture even from sparse (low-coverage) DNA contact information. Here we applied the RPR method to analyzing published scHi-C data of diploid cells derived from early-stage F1hybrid embryos . We found that paternal and maternal chromosomes become gradually intermingled from 1 cell to 64 cell stage and that discrete chromosome territories (CTs) are largely established between 8 cell and 64 cell stages. We also observed Rabl-like polarized distribution of chromosomes from 2 cell to 8 cell stage but this polarization becomes mostly dissolved by 64 cell stage. The formation of Rabl-like configuration precedes rod-like extension of the chromosomal shape and their parallel alignment, implicating a role of Rabl-like configuration in avoiding entanglement and promoting effective mixing of chromosomes before establishment of CTs. We also found a cell-to-cell variability in chromatin configuration. Combination of scHi-C and RPR analyses thus can characterize distinct 3D chromatin architecture of individual cells at different developmental stages during early embryogenesis.
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