Chromosome Intermingling: Mechanical Hotspots for Genome Regulation

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.