Chromosomes’ smallest structure revealed

To fit in a cell nucleus, DNA must be folded to a size orders of magnitude smaller than its stretched length. In the first step of that compaction, a DNA strand winds around 10-nm protein clusters to form units called nucleosomes. Cell biology textbooks typically show the nucleosomes closely and evenly spaced along the DNA strand, like pearls on a string. Now, using superresolution microscopy (see Physics Today, December 2014, page 18 ), Melike Lakadamyali , Maria Pia Cosma , and their colleagues at the Institute of Photonic Sciences and the Center for Genomic Regulation, both in Barcelona, Spain, have disproven that tidy picture. The researchers were initially interested in how chromosome structure differs between ordinary (or somatic) cells and stem cells. But when they took their first images of somatic cell nuclei, with the nucleosomes fluorescently labeled, what they saw was completely unexpected. Instead of showing the continuous fibers that they anticipated, their images were blotchy and heterogeneous, as seen in the figure. Although individual nucleosomes couldn’t be resolved, sophisticated numerical analysis showed that they were grouped into clusters, which the researchers call “clutches,” with a median size of 8 nucleosomes. In stem cells, the researchers again saw evidence of clutches, but with median sizes between 2 and 4. They don’t yet know whether the clutch size is a cause or a consequence of the cell type; to find out, they hope to study how the clutches change with time as stem cells differentiate into somatic cells—and as somatic cells treated with drugs are “reprogrammed” into stem cells. (M. A. Ricci et al., Cell 160, 1145, 2015 .)