A chromosome folding intermediate at the condensin-to-cohesin transition during telophase.,Nature Cell Biology

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A chromosome folding intermediate at the condensin-to-cohesin transition during telophase.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-11-04 , DOI: 10.1038/s41556-019-0406-2
Kristin Abramo ₁ , Anne-Laure Valton ₁ , Sergey V Venev ₁ , Hakan Ozadam ₂ , A Nicole Fox _{1,

3} , Job Dekker _{1,

3}

Affiliation

Chromosome folding is modulated as cells progress through the cell cycle. During mitosis, condensins fold chromosomes into helical loop arrays. In interphase, the cohesin complex generates loops and topologically associating domains (TADs), while a separate process of compartmentalization drives segregation of active and inactive chromatin. We used synchronized cell cultures to determine how the mitotic chromosome conformation transforms into the interphase state. Using high-throughput chromosome conformation capture (Hi-C) analysis, chromatin binding assays and immunofluorescence, we show that, by telophase, condensin-mediated loops are lost and a transient folding intermediate is formed that is devoid of most loops. By cytokinesis, cohesin-mediated CTCF-CTCF loops and the positions of TADs emerge. Compartment boundaries are also established early, but long-range compartmentalization is a slow process and proceeds for hours after cells enter G1. Our results reveal the kinetics and order of events by which the interphase chromosome state is formed and identify telophase as a critical transition between condensin- and cohesin-driven chromosome folding.

中文翻译：

末期凝缩蛋白到粘连蛋白转变的染色体折叠中间体。

随着细胞在细胞周期中的进展，染色体折叠受到调节。在有丝分裂期间，凝缩蛋白将染色体折叠成螺旋环阵列。在间期，粘连蛋白复合物生成环和拓扑关联域 (TAD)，而单独的区室化过程则驱动活性和非活性染色质的分离。我们使用同步细胞培养物来确定有丝分裂染色体构象如何转变为间期状态。使用高通量染色体构象捕获（Hi-C）分析、染色质结合测定和免疫荧光，我们表明，到末期，凝缩蛋白介导的环丢失，并形成缺乏大多数环的瞬时折叠中间体。通过胞质分裂，粘连蛋白介导的 CTCF-CTCF 环和 TAD 的位置出现。区室边界也在早期建立，但长程区室化是一个缓慢的过程，并且在细胞进入 G1 后持续数小时。我们的结果揭示了形成间期染色体状态的动力学和事件顺序，并将末期确定为凝聚蛋白和粘连蛋白驱动的染色体折叠之间的关键转变。

更新日期：2019-11-04

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