Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex three-dimensional structures. Fueled by a growing collection of sequencing and imaging-based technologies, studies have uncovered a hierarchy of DNA interactions, from small chromatin loops that connect genes and enhancers to larger topologically associated domains (TADs) and compartments. However, despite the remarkable conservation of these organizational features, we have a very limited understanding of how this organization influences gene expression. This issue is further complicated in the context of single-cell heterogeneity, as has recently been revealed at both the level of gene activation and chromatin topology. Here, we provide a perspective on recent studies that address cell-to-cell variability and the relationship between structural heterogeneity and gene expression. We propose that transcription is regulated by variable 3D structures driven by at least two independent and partially redundant mechanisms. Collectively, this may provide flexibility to transcriptional regulation at the level of individual cells as well as reproducibility across whole tissues.

中文翻译：

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单细胞分析突破了TAD形成和功能的界限。

真核基因组以其线性序列编码遗传信息，但是其基因的适当表达需要染色体折叠成复杂的三维结构。在越来越多的基于测序和成像技术的推动下，研究发现了DNA相互作用的层次结构，从将基因和增强子连接到较大的拓扑相关域（TAD）和区室的小的染色质环开始。然而，尽管这些组织特征得到了显着的保护，但是我们对这种组织如何影响基因表达的了解非常有限。在单细胞异质性的背景下，这个问题变得更加复杂，正如最近在基因激活和染色质拓扑学水平上所揭示的那样。这里，我们为处理细胞间变异性以及结构异质性与基因表达之间关系的最新研究提供了一个视角。我们提出转录受至少两个独立且部分冗余的机制驱动的可变3D结构调控。总体而言，这可以为单个细胞水平的转录调控提供灵活性，并为整个组织提供可重复性。