The fine art of chromatin folding: Revealing the path of DNA inside mitotic chromosomes

How chromatin fibers fold into rod-shaped mitotic chromosomes has long been a central question in genome biology. Two new studies now reconstruct the path of DNA in human chromosomes at nanoscale resolution and reveal how loop-extruding molecular machines fold chromatin into compact, rod-shaped structures at the onset of mitosis. Using microscopy- or sequencing-based approaches, respectively, both studies converge on similar models of chromosome organization yet differ in key mechanistic details. The findings further challenge textbook hypotheses of higher-order chromatin structures and reignite the quest for a detailed understanding of genome architecture inside living cells.