Visualizing the Organization of Mitotic Chromosomes by Super-resolution Microscopy

Chromosome folding is one of the most dramatic events in cells. In 40 minutes, nearly two meter-long DNA are reorganized completely into 46 highly condensed chromosomes in human mitotic cells. Yet, the underlying mechanisms remain elusive. We have developed a novel super-resolution microscopy, which integrates expansion microscopy (ExM) with STORM/PALM and reaches sub-10-nm resolution in 3D, bringing the resolution of optical microscopy into the regime of electron microscopy. The new super-resolution microscopy provides the first direct visualization of a multi-helical architecture within a chromosome, and imply a novel cooperative folding mechanism by condensin and topoisomerase IIalpha.