Fig. 1.

Model: Mechanical force is critical for normal genome organization. Top left: Wild type cells exhibit normal force transduction to the nucleus via the LINC complex and have normal LADs at the nuclear periphery. Top right: Cells with perturbations of the nuclear lamina via mutations in LMNA feature compromised LADs and aberrant upregulation of non-lineage genes. Bottom right: Cells with perturbations to the LINC complex via SUN1 deletion may demonstrate compromised LAD organization, leading to aberrant gene expression and failure to properly respond to mechanical stimuli. Bottom left: Perturbation of the LINC complex in LMNA mutant conditions may preserve LAD organization and prevent abnormal gene expression, based on observations of Lmna mutant defects (partially) ameliorated with concomitant SUN1 loss. Figure created with BioRender.com