We study the structural ensembles of human chromosomes across different cell types. Using computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin structures obtained through microscopy. We demonstrate using a combination of machine learning and polymer physics simulations that epigenetic information can be used to predict the structural ensembles of multiple human cell lines. The chromosomal structures obtained in silico are quantitatively consistent with those obtained through microscopy as well as DNA-DNA proximity ligation assays. 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 transitions between a closed conformation and an open dumbbell conformation. This conformational transition appears to be consistent with a two-state process with an effective free energy cost of about four times the effective information theoretic temperature. Finally, we study the conformational changes associated with the switching of genomic compartments observed in human cell lines. Genetically identical but epigenetically distinct cell types appear to rearrange their respective structural ensembles to expose segments of transcriptionally active chromatin, belonging to the A genomic compartment, towards the surface of the chromosome, while inactive segments, belonging to the B compartment, move to the interior. 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.

中文翻译：

---

探索跨多个细胞系的染色体结构异质性

我们研究了跨不同细胞类型的人类染色体的结构整体。使用计算机模拟，我们生成了特定于细胞的3D染色体结构，并将其与最近通过显微镜获得的染色质结构进行了比较。我们证明结合使用机器学习和高分子物理模拟，表观遗传信息可用于预测多个人类细胞系的结构体。在硅胶上获得的染色体结构与通过显微镜以及DNA-DNA邻近连接分析获得的结果在数量上一致。理论预测染色体结构是可变的，只能由一个整体描述，这与观察到染色体没有独特的折叠相一致。尽管如此，我们通过仿真和显微镜对这两种结构的分析表明，染色质的短片段在闭合构象和开放哑铃构象之间进行过渡。这种构象转变似乎与两态过程一致，其有效自由能成本约为有效信息理论温度的四倍。最后，我们研究了与人类细胞系中观察到的基因组区室转换相关的构象变化。遗传上相同但表观遗传上不同的细胞类型似乎重新排列了它们各自的结构集合，从而使属于A基因组区室的转录活性染色质片段向染色体表面暴露，而属于B区室的无活性片段向内部移动。 。基因组区室的形成类似于蛋白质折叠中的疏水性塌陷，其中密集且主要是无活性的染色质的聚集驱动着活性染色质朝向各个染色体区域的表面定位。移到内部。基因组区室的形成类似于蛋白质折叠中的疏水性塌陷，其中致密的染色质（主要是无活性的）的聚集驱动着活性染色质朝向各个染色体区域的定位。移到内部。基因组区室的形成类似于蛋白质折叠中的疏水性塌陷，其中致密的染色质（主要是无活性的）的聚集驱动着活性染色质朝向各个染色体区域的定位。