Chromosome folding

Stretched out completely, a human chromosome would be several centimeters long. It is packed, along with its 45 companions, into a few-microns-wide cell nucleus in such a way that all the necessary genes are accessible to RNA transcription. Figuring out how that packing is done is no easy task. Microscopy helps, but provides nowhere near a complete picture. Now a research team led by Eric Lander of MIT and Job Dekker of the University of Massachusetts has developed a method for probing chromosomes’ folded structures. The researchers chemically join segments of a folded chromosome that are close in space, cut away and sequence the DNA around the crosslink, and compare those sequences to genome libraries to determine which parts of the chromosome are in contact. A matrix of the observed contacts, as shown in the figure, reveals large-scale organization. Analyzing the plaid pattern, the researchers found that most of the cell’s actively transcribed DNA was spatially segregated from most of the inactive DNA. On a smaller scale, chromosome segments a millimeter or so in extended length appeared to form so-called fractal globules with self-similar structures very different from that of a tangled polymer in equilibrium. So far, the researchers have studied only cultured cell lines: one derived from a tumor and another modified by a virus. They hope to apply their method to healthy cells and to look for differences in chromosome structure among cells of different types. (E. Lieberman-Aiden et al., Science 326, 289, 2009 .) --Johanna Miller