How Are Chromosomes Packed During Cell Division?

A research group led by Daniel W. Gerlich, Senior Scientist at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), discovered a molecular mechanism that imparts special physical properties to chromosomes in dividing human cells, allowing them to be transmitted securely to future generations.

Novel Molecular Mechanism Enables Chromosomes to Prevent Microtubule Perforation

During cell division, a copy of a genome must be accurately transported to two daughter cells. In order to perform genome segregation accurately, extremely long chromosomal DNA molecules need to be “packed” into discrete nucleosomes that can be efficiently transported by a large number of spindles composed of microtubules.

Previous studies have found that chromatin fibers are folded into rings by condensin during cell division. However, the effect of condensin alone does not explain why chromosomes appear as compacted bodies with sharp surface boundaries rather than becoming more loosely structured.

Although other studies have also shown that histone acetylation is associated with the regulation of chromosome compaction during cell division, the relationship between histone acetylation and condensins, as well as the functional correlation between them still remains unclear.

With the latest study, the team believes that they have gained some conceptual understanding of both mechanisms: everything is related to how the chromosomes are transmitted to the offspring precisely.

The Relationship Between Condensin and Histone Acetylation

In the latest study published in Nature, the team altered the levels of condensins and histone acetylation to investigate the effects of both. The results showed that while removing condensins disrupted the elongated shape of chromosomes in dividing cells and reduced their resistance to tension, it did not affect their degree of compactness. However, if the level of histone acetylation was increased in parallel with the depletion of condensins, it resulted in the breakdown of a large amount of chromatin in dividing cells and the perforation of chromosomes by microtubules.

Based on the observations, the researchers hypothesized that chromatins are organized into an expanded gel for most of the cell cycle and that this gel is compressed into a less soluble form when the overall level of acetylation decreases as the cell divides. The team then also divided the mitotic chromosomes into smaller pieces to further investigate the solubility of chromatin.

The observations support the model that when acetylation levels are reduced overall during mitosis, chromatin becomes an insoluble gel with a sharp surface boundary, providing a physical basis for resistance to microtubule perforation. Subsequent experiments and observations revealed that the insoluble chromatin formed a negatively charged compact structure that excluded negatively charged macromolecules and microtubules.

The researchers believe that this study provides a unified view of how chromatin looping by condensin and compaction through a phase transition driven by acetylation-sensitive nucleosome interactions contribute to mitotic chromosomes’ material properties and mechanical functions. It will be interesting to further investigate how chromatin adapts its material properties to other physiological processes that involve compaction, such as apoptosis.

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