Cell-cycle dynamics of chromosomal organization at single-cell resolution.

Cell-cycle dynamics of chromosomal organization at single-cell resolution.
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单细胞分辨率下染色体组织的细胞周期动力学。

DOI:
10.1038/nature23001
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发表时间:
2017-07-05
期刊:
影响因子:
64.8
通讯作者:
Tanay A
Tanay A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Nagano T;Lubling Y;Várnai C;Dudley C;Leung W;Baran Y;Mendelson Cohen N;Wingett S;Fraser P;Tanay A

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增殖后生动物细胞中的染色体在每个细胞周期都经历戏剧性的结构变态,在促进染色体分离的高度浓缩的有丝分裂结构和容纳转录、基因沉默和DNA复制的解浓缩的间期结构之间交替。在这里,我们使用单细胞Hi-C来研究数千个单个细胞中的染色体构象,并发现顺式相互作用的连续谱,这些谱精细地将单个细胞沿着细胞周期定位。我们发现,染色体车厢,拓扑相关域(TADs),接触绝缘和长程循环,所有定义的散装高碳地图,是由不同的细胞周期动力学。特别是,DNA复制与隔室的建立和细胞绝缘的减少相关,而环通常从G1到S和G2是稳定的。全基因组3D结构模型揭示了具有不同表观基因组特征的染色体区室的放射状结构。因此,我们的单细胞数据允许通过细胞周期的棱镜重新解释染色体构象图。
Chromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between highly condensed mitotic structures facilitating chromosome segregation, and decondensed interphase structures accommodating transcription, gene silencing and DNA replication. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological associated domains (TADs), contact insulation and long-range loops, all defined by bulk Hi-C maps, are governed by distinct cell-cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Whole-genome 3D structural models reveal a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data thereby allow for re-interpretation of chromosome conformation maps through the prism of the cell cycle.
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期刊: NATURE
影响因子: 64.8
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期刊: Science (New York, N.Y.)
影响因子: --
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