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^1,2,3. Assembly of mitotic chromosomes involves DNA looping by condensin^4,5,6,7,8 and chromatin compaction by global histone deacetylation^{9,10,11,12,13}. Although condensin confers mechanical resistance to spindle pulling forces^14,15,16, 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.

分裂真核细胞将极长的染色体 DNA 分子包装成离散的小体，以使微管介导的一个基因组拷贝转运到每个新形成的子细胞^1,2,3。有丝分裂染色体的组装涉及通过凝聚素^{4、5、6、7、8}形成的 DNA 循环和通过全局组蛋白去乙酰化^{9、10、11、12、13}进行的染色质压实。尽管凝聚素对主轴拉力具有机械阻力^14,15,16，尚不清楚组蛋白去乙酰化如何影响材料特性，从而影响有丝分裂染色体的分离机制。在这里，我们展示了有丝分裂开始时的全局组蛋白去乙酰化如何诱导染色质内在相变，从而赋予染色体在细胞分裂过程中精确运动所需的物理特征。去乙酰化介导的染色质压实形成负电荷密集的结构，并允许有丝分裂的染色体在微管被推到中期板时抵抗微管的穿孔。相比之下，高乙酰化的有丝分裂染色体缺乏明确的表面边界，经常被微管穿孔并且容易发生错误分离。