A chromatin phase transition protects mitotic chromosomes against microtubule perforation

Schneider, M. W. G.; Gibson, B. A.; Otsuka, S.; Spicer, M. F. D.; Petrovic, M.; Blaukopf, C.; Langer, C. C. H.; Doolittle, L. K.; Rosen, M. K.; Gerlich, D. W.

doi:10.1101/2021.07.05.450834

bioRxiv · 10.1101/2021.07.05.450834

A chromatin phase transition protects mitotic chromosomes against microtubule perforation

Schneider, M. W. G.·Gibson, B. A.·Otsuka, S.·Spicer, M. F. D.·Petrovic, M.·Blaukopf, C.·Langer, C. C. H.·Doolittle, L. K.·Rosen, M. K.·Gerlich, D. W.

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Abstract

Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells1-3. Assembly of mitotic chromosomes involves DNA looping by condensin4-8 and chromatin compaction by global histone deacetylation9-13. While condensin confers mechanical resistance towards spindle pulling forces14-16, it is not known how histone deacetylation affects material properties and segregation mechanics of mitotic chromosomes. Here, we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with specific characteristics necessary for their precise movement during cellular division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. Hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules, and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin-intrinsic phase separation to genome segregation in dividing cells.

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Schneider, M. W. G., Gibson, B. A., Otsuka, S., Spicer, M. F. D., Petrovic, M., Blaukopf, C., Langer, C. C. H., Doolittle, L. K., Rosen, M. K., Gerlich, D. W.. 2021-07-05. A chromatin phase transition protects mitotic chromosomes against microtubule perforation. https://doi.org/10.1101/2021.07.05.450834

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