Picturing the organization of mitotic chromosomes

Chromosomes, with their tightly coiled but elongated X-shaped profile, are among the most recognizable features of a dividing cell. But how DNA is organized inside the chromosomes is largely unresolved. Although a chromosome may look hopelessly tangled, there exist distinct patterns in how it contorts and arranges itself. Methods known collectively as chromosome conformation capture, first developed by Job Dekker of the University of Massachusetts Medical School and colleagues a decade ago, offer a way to examine the folded conformations by chemically linking parts of the chromosome that are spatially close. Sequencing the linked DNA segments allowed the researchers to figure out which parts of the chromosome are likely to have intersected. The result was a map of contact points at which segments of base pairs fold inside a nucleus (see Physics Today, December 2009, page 19 ). Dekker, Leonid Mirny (MIT), and their colleagues have now combined chromosome conformation capture with polymer simulations of DNA to model how a chromosome disassembles and then reassembles itself during mitosis. They found that as the cell nucleus is dissolved, chromosomes become reorganized in two phases. First, the long chromosome fiber of protein and DNA compacts itself into an array of consecutive loops of some 80 000 to 120 000 base pairs that emanate from and return to a central scaffold—the flexible, dark-colored rod pictured here. That phase is then followed by axial compression of the scaffold to form a short, dense cylinder. (For a movie that illustrates the process, see the online version of this update.) Yet to be understood is what interactions guide the reorganization. (N. Naumova et al., Science 342, 948, 2013, doi:10.1126/science.1236083 .)