Nuclear envelope proteins regulate chromosome territory and gene loci dynamics in the interphase nucleus

Abstract

It is well established that chromosome territories are non-randomly organized in the interphase nucleus, with gene poor chromosome territories proximal to the nuclear periphery, while gene rich chromosome territories are closer to the nuclear center. Such an organization is conserved in evolution. We showed that the depletion of the nuclear envelope proteins i.e, lamins, not only induces chromosomal instability but also destabilizes chromosome positioning in otherwise diploid colorectal cancer cells. Remarkably, the combined loss of lamins and Emerin perturb chromosome territory and gene loci dynamics in the interphase nucleus. Furthermore, nuclear envelope proteins are essential for relaying mechanical signals into the nucleus, since cells cultured on softer substrates showed a striking change in the spatial organization of chromosome territories in an Emerin-Lamin dependent manner. Taken together, our studies reveal an overarching role for nuclear envelope proteins, in the maintenanc...