Emilie Lukášová, Aleš Kovařík and Stanislav Kozubek
An important mechanism ensuring spatial organization of chromatin structure and genome function in eukaryotic nuclei consists in anchoring of specific heterochromatin regions to nuclear envelope by proteins of inner nuclear membrane (INM) that are able to recognize these regions and simultaneously bind either Lamin A/C or lamin B1. One of these proteins is lamin B receptor (LBR) that binds lamin B1 and tethers heterochromatin to INM in embryonic and undifferentiated cells. It is replaced by lamin A/C with specific lamin A/C binding proteins (especially LEM-domain proteins) at the beginning of cell differentiation. Our functional experiments in cancer cell lines show that heterochromatin in cancer cells is tethered to INM by LBR that is downregulated together with lamin B1 at the onset of cell transition to senescence. A coordinated regulation of these proteins is evidenced also by downregulation of LB1 in cells with LBR silenced by shRNA. The downregulation of these proteins in senescent cells leads to the detachment of centromeric heterochromatin from INM resulting in it distension in nucleoplasm. These changes in structure of constitutive heterochromatin may be the reason of a permanent loss of cell proliferation in senescence.