Genome Organization and Chromosome Architecture.

How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes, and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The solution to this question presented here rests on the correlations that were found to hold between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. The key points are the following: (1) The transition from the looped domains and subdomains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through their unfolding into an extended chromatin structure (probably a 10-nm "beads-on-a-string" structure); (2) the architectural proteins of interphase chromatin, such as CTCF and cohesin subunits, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; and (3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the reversibility of the interphase to mitosis process and the "mitotic memory" of interphase architecture.