Role of Cell Geometry on Nuclear Mechanics, Chromosome Reorganization, and Gene Expression

In this book chapter, we summarize the current findings for the physical and chemical connections between the extracellular matrix (ECM) and 3D chromosome organization, which ultimately lead to modular gene regulation. An overview is first provided to delineate the linkage between the nucleoskeleton and cytoskeleton through LINC complexes and on how this linkage regulates nuclear mechanotransduction. This involves alterations in nuclear morphology and dynamics, by reorganization of cytoskeletal network and actomyosin contractility in response to different ECM constraints. These external mechanical signals, once transduced to the nucleus, facilitate remodeling of chromatin dynamics, epigenetic landscape, and 3D chromosome organization. Finally, we present the role of cell geometric constraints on 3D chromosome organization for modulating gene expression. Extreme alterations in matrix signals could lead to a number of diseases, including fibrosis and cancer. In this context, analysis of nuclear mechanotransduction and genome regulation could provide a better understanding of tissue homeostasis.