A. Rosa, M. Di Stefano and C. Micheletti
Topological Constraints in Eukaryotic Genomes and How They Can Be Exploited to Improve Spatial Models of Chromosomes
Front. Mol. Biosci., 2019, 6 , 127
Link to online article

Opinion article. -- From the introduction:
From viruses to eukaryotes, genomic DNA filaments are confined in spaces of linear dimension much smaller than their contour lengths. In bacteriophages, the μm-long genome is stored in 50 nm-wide viral capsids and the corresponding packing density is so high that viral DNA filaments that have little chance to be entangled in solution (knotting probability <3%) become almost certainly knotted (>95% probability) once confined inside the capsid. In humans, instead, the various cm-long chromosomes that make up the genome are kept inside 10 μm-wide nuclei. Despite the major change of scale with respect to viruses, the volume fraction occupied by this eukaryotic genome is still large, about 10%. These considerations pose several conundrums: How can chromosomal DNA be at the same time packed and yet accessible to the regulatory and transcriptional machineries? What is its typical degree of genomic entanglement and how much does it interfere with DNA transactions? To what extent are these aspects shaped by general passive physical mechanisms vs. active ones, e.g., involving topoisomerase enzymes?