Three-dimensional (3D) chromatin organization plays a key role in regulating mammalian genome function, however many of its physical features at the single-cell level remain underexplored. Here we use 3D super-resolution and scanning electron microscopy to analyze structural and functional nuclear organization in somatic cells. We identify linked chromatin domains (CDs) composed of irregular ~200-300-nm-wide aggregates of nucleosomes that can overlap with individual topologically associating domains and are distinct from a surrounding RNA-populated interchromatin region. High-content mapping uncovers confinement of cohesin and active histone modifications to surfaces and enrichment of repressive modifications towards the core of CDs in both hetero- and euchromatic regions. This nanoscale functional topography is temporarily relaxed in post-replicative chromatin, but remarkably persists after ablation of cohesin. Our findings establish CDs as physical and functional modules of mesoscale genome organization.

中文翻译：

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染色质排列在中尺度结构域的链中，具有独立于黏附素的纳米尺度功能拓扑

三维（3D）染色质组织在调节哺乳动物基因组功能中起关键作用，但是在单细胞水平上其许多物理特征仍未得到充分研究。在这里，我们使用3D超分辨率和扫描电子显微镜来分析体细胞中的结构和功能性核组织。我们确定链接的染色质域（CDs）组成的核小体的不规则〜200-300 nm宽的聚集体，可以与单个拓扑关联域重叠，并且与周围的RNA填充染色质间区域不同。高含量的映射揭示了粘着蛋白的限制和表面的活性组蛋白修饰，以及异染色质和常色区中对CD核心的抑制性修饰的富集。该纳米级功能拓扑在复制后的染色质中暂时松弛，但在黏附素消融后仍显着存在。我们的发现将CD确立为中尺度基因组组织的物理和功能模块。