Cells sense physical and chemical signals from their local microenvironment and transduce them to the nucleus to regulate genomic programs. In this review, we first discuss different modes of mechanotransduction to the nucleus. We then highlight the role of the spatial organization of chromosomes for integrating these signals. In particular, we emphasize the importance of chromosome intermingling for gene regulation. We also discuss various geometric models and recent advances in microscopy and genomics that have allowed access to these nanoscale chromosome intermingling regions. Taken together, the recent work summarized in this review culminates in the hypothesis that chromosome intermingling regions are mechanical hotspots for genome regulation. Maintenance of such mechanical hotspots is crucial for cellular homeostasis, and alterations in them could be precursors for various cellular reprogramming events, including diseases.

细胞从其局部微环境感知物理和化学信号，并将其转导至细胞核以调节基因组程序。在这篇综述中，我们首先讨论了机械传递至细胞核的不同模式。然后，我们强调了染色体空间组织对于整合这些信号的作用。特别是，我们强调了染色体混合对于基因调控的重要性。我们还讨论了各种几何模型以及显微镜和基因组学的最新进展，这些进展已允许访问这些纳米级染色体混杂区域。综上所述，本综述总结的最新工作最终得出以下假设，即染色体混合区是基因组调控的机械热点。维护此类机械性热点对于细胞体内平衡至关重要，