The higher-order structure in the cells nucleus as the structural basis of the post-mitotic state

In metazoan cells during the interphase nuclear DNA is organized in supercoiled, topologically constrained loops anchored to a proteinaceous compartment or substructure commonly known as the nuclear matrix (NM). The DNA-NM interactions result from a thermodynamically-driven process leading to the necessary dissipation of structural stress along chromosomal DNA, otherwise the chromosomes would break into pieces. Such DNA-NM interactions define a nuclear higher-order structure that is independent of chromatin proteins. On the other hand, a metazoan cell no longer able to undergo mitosis is defined as post-mitotic and this condition indicates a terminally differentiated cell that may survive in such a state for indefinite time. The non-reversible nature of the post-mitotic state suggests a non-genetic basis for it since no spontaneous or induced mutations can revert it. Yet in individual cells the loss of proliferative potential has both a developmental and a stochastic component. Here we discuss evidence suggesting that the stability of the nuclear higher-order structure is the factor that links the stochastic and developmental components leading to the post-mitotic state.