Energy landscape analysis of the development of the chromosome structure across the cell cycle

During mitosis, there are significant structural changes in chromosomes. We used a maximum entropy approach to invert experimental Hi-C data to generate effective energy landscapes for chromosomal structures at different stages during the cell cycle. Modeled mitotic structures show a hierarchical organization of helices of helices. High-periodicity loops span hundreds of kilobases or less, while the other low-periodicity ones are larger in genomic separation, spanning several megabases. The structural ensembles reveal a progressive decrease in compartmentalization from interphase to mitosis, accompanied by the appearance of a second diagonal in prometaphase, indicating an organized array of loops. While there is a local tendency to form chiral helices, overall, no preferential left-handed or right-handed chirality appears to develop on the time scale of the cell cycle. Chromatin thus appears to be a liquid crystal containing numerous defects that anneal rather slowly.