Exploring chromosomal structural heterogeneity across multiple cell lines.
Exploring chromosomal structural heterogeneity across multiple cell lines.
复制标题
探索多个细胞系的染色体结构异质性。
DOI：
10.7554/elife.60312
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发表时间：
2020-10-13
期刊：
影响因子：
7.7
通讯作者：
Onuchic JN
中科院分区：
文献类型：
--
作者：
Cheng RR;Contessoto VG;Lieberman Aiden E;Wolynes PG;Di Pierro M;Onuchic JN
使用计算机模拟，我们生成细胞特异性的3D染色体结构，并将其与最近发表的通过显微镜获得的染色质结构进行比较。我们使用机器学习和高分子物理模拟证明，表观遗传信息可用于预测多种人类细胞系的结构集合。理论预测，染色体结构是流体，只能用系综来描述，这与染色体没有独特折叠的观察结果一致。然而，我们的分析表明，这两个结构从模拟和显微镜染色质的短片段之间的封闭构象和开放哑铃构象的两个状态转换。最后，我们研究了与人类细胞系中观察到的基因组区室切换相关的构象变化。基因组区室的形成类似于蛋白质折叠中的疏水性塌陷，其中较致密且主要无活性的染色质的聚集驱动活性染色质朝向个体染色体区域的表面定位。
Using computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin structures obtained through microscopy. We demonstrate using machine learning and polymer physics simulations that epigenetic information can be used to predict the structural ensembles of multiple human cell lines. Theory predicts that chromosome structures are fluid and can only be described by an ensemble, which is consistent with the observation that chromosomes exhibit no unique fold. Nevertheless, our analysis of both structures from simulation and microscopy reveals that short segments of chromatin make two-state transitions between closed conformations and open dumbbell conformations. Finally, we study the conformational changes associated with the switching of genomic compartments observed in human cell lines. The formation of genomic compartments resembles hydrophobic collapse in protein folding, with the aggregation of denser and predominantly inactive chromatin driving the positioning of active chromatin toward the surface of individual chromosomal territories.