“The extrusion of loops by motors, as is often the case in biology, is random: they constantly form and disappear. This, in particular, explains why their experimental detection in a single living cell is so difficult. We took a different approach: we developed a physical theory that shows how randomly distributed loops on a polymer would affect the spatial organization of the polymer. Next, we analyzed experimental data on the spatial packing of chromosomes obtained on billions of living cells and found the same statistical features there,” says Kirill Polovnikov, the leading author of the study, an assistant professor, and the head of the research group at Skoltech.
The developed theory has allowed determining the typical size of chromosomal loops and their density. In addition, the authors have discovered a new topological effect associated with loops. When the loops are extruded, the backbone of the chain shortens, however, it stretches out in the three-dimensional space due to the so-called “dilution of entanglements” effect in the polymer system. The scientists have developed an analytical model of this effect and also confirmed their results in computer simulations. The theory helps identify and characterize chromosomal loops using experimental data and changes our understanding of the topological organization of chromosomes in a living cell.
“Just as astrophysicists find new exoplanets by the decrease of the luminosity of the parent star during the passage of the planet, our theory offers a tool for detecting the ‘trace’ of loops in the genomic data. Surprisingly, the identified characteristics turn out to be universal not only for humans, but also for the cells of other organisms. Apparently, the folding of chromosomes into loops is one of the most general principles of the spatial organization of DNA,” adds Kirill Polovnikov.
The research was supported by the Russian Scientific Foundation under grant No. 21-73-00176 titled “Effects of topological interactions and active loop extrusion in regulation of spatial organization of chromosomes”.