Reproducible but dynamic positioning of DNA in chromosomes during mitosis

How DNA is folded into chromosomes is unknown. Mitotic chromosome banding s hows reproducibility in longitudinal compaction at a resolution of several megabase pairs, but it is less clear whether DNA sequences are targeted lat erally to specific locations. The in vitro chromosome assembly of prokaryot ic DNA(1) suggests that there is a lack of sequence requirements for chromo some condensation, implying an absence of DNA targeting. Protein extraction experiments indicate, however, that specific DNA sequences may bind to a c hromosome scaffold(2,3). Chromosome banding patterns, using dyes with diffe rential sequence specificity, have been interpreted to result from the alig nment of AT-rich sequences in a partially helically folded chromosome scaff old(4). But fluorescence in situ hybridization experiments, perhaps owing t o technical limitations, have shown at best only slight deviation from a ra ndom, lateral sequence distributions. Here we show that there is highly rep roducible targeting of specific chromosome segments to the metaphase chroma tid axis, but that these segments localize to the periphery of prophase and telophase chromosomes. Unfolding intermediates during anaphase and telopha se suggest that sequence repositioning occurs through the global uncoiling of an underlying chromatid structure.