Emergent coiling of chromosomes

When completely stretched, chromosomes can extend to several centimeters in length. Multiple levels of compaction are therefore required to fit the genome into the cell nucleus in an organized manner and to further condense it for the faithful segregation of genetic material during the cell cycle. Despite more than a century of observations and hypotheses, predating even the discovery of DNA itself, the mechanisms underlying chromosome compaction remain incompletely understood. Over the last decade, advances in sequencing technologies have revealed loop formation as a fundamental mechanism of chromosome compaction, modulated across different stages of the cell cycle. At metaphase, chromosomes appear highly compacted and frequently display a further coiled, helical organization [1]. Yet the origin of which remains unclear. Polymer models suggest that fully looped chromosomes adopt a worm-like, prophase-like conformation resembling the chromatin thread historically described as the chromonema in early microscopy studies [2]. We hypothesize that the chromonema possesses intrinsic topological properties and that chromosome coiling may emerge as a passive response of the chromonema to mechanical and spatial constraints of the cellular environment, rather than from an active process. Using polymer simulations, we impose different constraint regimes on chromonema-like segments and compare the resulting conformations with chromosome conformation capture sequencing data and super-resolution imaging of chromosomes at multiple stages of the cell cycle. Our results support a physically grounded mechanism for the emergence of helical chromosome organization during mitotic compaction.

References

[1] Kubalová, et al. Helical coiling of metaphase chromatids. Nucleic Acids Research, 2023.

[2] Câmara, et al. Helical chromonema coiling is conserved in eukaryotes. The Plant Journal, 2024.