Inserted DNA folds hierarchically into condensed chromosomes.

As cells progress from interphase through metaphase, their chromosomes undergo structural changes that are easy to observe but difficult to understand. Strukov et al. (page 23) attacked this problem by engineering chromosome regions that can be labeled selectively, allowing the authors to analyze chromosome condensation at high resolution. Their initial results provide strong support for one model of chromosome folding while contradicting predictions of another.

Previous work has supported two different models of chromosome condensation. In the radial loop model, scaffold/matrix-associated region (SAR/MAR) sequences in DNA anchor portions of the chromosome to a central scaffold, producing loops of 30-nm fibers. In the hierarchical folding model, however, there is a continuum of folding steps, independent of the SAR/MAR sequences, that produces more complicated structures than the 30-nm loops.

In the new work, the authors created chromosome regions containing large copy numbers of a vector containing SAR/MAR sequences flanking lac operator repeats. Staining with lac repressor showed that the SAR sequences are not specifically targeted to the chromatid axis, contradicting predictions of the radial loop model. Closer analysis revealed a 250-nm diameter coiling subunit within native metaphase chromosomes, strongly supporting the hierarchical folding model. The authors are now trying to improve the resolution of the system even further, and hope to analyze the entire process of chromosome condensation. ▪