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有丝分裂向间期转变过程中的全基因组结构的三维模拟。

Three-Dimensional Simulation of Whole-Genome Structuring Through the Transition from Anaphase to Interphase.

机构信息

Fukui Institute for Fundamental Chemistry, Kyoto University, Kyoto, Japan.

Department of Complex Systems Science, Nagoya University, Nagoya, Japan.

出版信息

Methods Mol Biol. 2025;2856:293-308. doi: 10.1007/978-1-0716-4136-1_18.

DOI:10.1007/978-1-0716-4136-1_18
PMID:39283460
Abstract

In order to analyze the three-dimensional genome architecture, it is important to simulate how the genome is structured through the cell cycle progression. In this chapter, we present the usage of our computation codes for simulating how the human genome is formed as the cell transforms from anaphase to interphase. We do not use the global Hi-C data as an input into the genome simulation but represent all chromosomes as linear polymers annotated by the neighboring region contact index (NCI), which classifies the A/B type of each local chromatin region. The simulated mitotic chromosomes heterogeneously expand upon entry to the G1 phase, which induces phase separation of A and B chromatin regions, establishing chromosome territories, compartments, and lamina and nucleolus associations in the interphase nucleus. When the appropriate one-dimensional chromosomal annotation is possible, using the protocol of this chapter, one can quantitatively simulate the three-dimensional genome structure and dynamics of human cells of interest.

摘要

为了分析三维基因组结构,模拟基因组如何随着细胞周期的进展而构建是很重要的。在本章中,我们介绍了如何使用我们的计算代码来模拟人类基因组的形成过程,即细胞从后期转变为间期的过程。我们没有将全局 Hi-C 数据作为基因组模拟的输入,而是将所有染色体表示为线性聚合物,这些聚合物由相邻区域接触指数(NCI)注释,该指数对每个局部染色质区域的 A/B 类型进行分类。模拟有丝分裂染色体在进入 G1 期时不均匀地扩张,这会导致 A 和 B 染色质区域的相分离,从而在间期核中建立染色体区域、隔室和板层以及核仁的关联。当可以使用适当的一维染色体注释时,可以使用本章中的协议来定量模拟感兴趣的人类细胞的三维基因组结构和动力学。

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Methods Mol Biol. 2025;2856:293-308. doi: 10.1007/978-1-0716-4136-1_18.
2
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本文引用的文献

1
Generation of dynamic three-dimensional genome structure through phase separation of chromatin.通过染色质相分离生成动态三维基因组结构。
Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2109838119. doi: 10.1073/pnas.2109838119. Epub 2022 May 26.
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Bottom-up modeling of chromatin segregation due to epigenetic modifications.由于表观遗传修饰导致的染色质分离的自下而上建模。
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Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.
转录因子通过其激活结构域的相分离能力激活基因。
Cell. 2018 Dec 13;175(7):1842-1855.e16. doi: 10.1016/j.cell.2018.10.042. Epub 2018 Nov 15.
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Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.HP1α形成液滴表明相分离在异染色质中起作用。
Nature. 2017 Jul 13;547(7662):236-240. doi: 10.1038/nature22822. Epub 2017 Jun 21.
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A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.一份碱基对分辨率的人类基因组三维图谱揭示了染色质环化的原理。
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Genome organization in and around the nucleolus.核仁内及周围的基因组组织。
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Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages.在有丝分裂和G1早期,HeLa细胞中的染色体顺序会发生变化,但在随后的间期阶段会稳定维持。
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