Progressive chromosome shape changes during cell divisions

Abstract

Mitotic chromosomes give genome portions the required compaction and mechanical stability for faithful inheritance during cell divisions. They are shaped by the chromosomal condensin complex. Here, we record human chromosome dimensions from their appearance in prophase over successive times in a mitotic arrest. Chromosomes first appear long and uniformly thin. Then, individual chromosome arms become discernible, which continuously shorten and thicken—the longer a chromosome arm, the thicker it becomes. In the search for a molecular explanation of this behavior, given uniform condensin density, the popular loop extrusion model provides no obvious means by which longer chromosome arms become thicker. Instead, we find that simulations of an alternative loop capture model recapitulate key features of our observations, with re-arranging chromatin rosettes underpinning the gradually developing arm length-to-width relationship. Our analyses portray chromosomes as out-of-equilibrium structures in the process of transitioning towards, but on biologically relevant time scales not typically reaching, steady state.