A mitotic chromatin phase transition prevents perforation by microtubules.
Maximilian W G SchneiderBryan A GibsonShotaro OtsukaMaximilian F D SpicerMina PetrovicClaudia BlaukopfChristoph C H LangerPaul BattyThejaswi NagarajuLynda K DoolittleMichael K RosenDaniel W GerlichPublished in: Nature (2022)
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 cells 1-3 . Assembly of mitotic chromosomes involves DNA looping by condensin 4-8 and chromatin compaction by global histone deacetylation 9-13 . Although condensin confers mechanical resistance to spindle pulling forces 14-16 , it is not known how histone deacetylation affects material properties and, as a consequence, 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 the physical characteristics necessary for their precise movement during cell 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. By contrast, 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 phase separation to genome segregation in dividing cells.
Keyphrases
- induced apoptosis
- genome wide
- gene expression
- transcription factor
- dna damage
- cell cycle
- dna methylation
- cell cycle arrest
- circulating tumor
- single molecule
- cell free
- endoplasmic reticulum stress
- magnetic resonance
- signaling pathway
- physical activity
- oxidative stress
- mesenchymal stem cells
- single cell
- cell therapy
- contrast enhanced