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有丝分裂的染色质相变可防止微管穿孔的发生
2022-08-06 23:44

奥地利科学院分子生物技术研究所Daniel W. Gerlich、Maximilian W. G. Schneider等研究人员合作发现,有丝分裂的染色质相变可防止微管穿孔的发生。相关论文于2022年8月3日在线发表在《自然》杂志上。

研究人员在有丝分裂开始时全局组蛋白去乙酰化如何诱导染色质内在相变,使染色体具有在细胞分裂过程中精确运动所需的物理特性。去乙酰化介导的染色质压实形成了一个负电荷密集的结构,使有丝分裂的染色体在被推到中期板时能抵御微管的穿孔。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,容易发生错位。这项研究强调了DNA环的形成和染色质相分离对分裂细胞中基因组分离的不同贡献。

据了解,分裂的真核细胞将极长的染色体DNA分子包装成离散体,以便在微管介导下将一个基因组拷贝运送到每个新形成的子细胞中。有丝分裂染色体的组装包括凝集蛋白对DNA的缠绕和全局组蛋白去乙酰化对染色质的压缩。尽管凝集蛋白赋予了对纺锤体拉力的机械阻力,但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力学,目前还不清楚。

附:英文原文

Title: A mitotic chromatin phase transition prevents perforation by microtubules

Author: Schneider, Maximilian W. G., Gibson, Bryan A., Otsuka, Shotaro, Spicer, Maximilian F. D., Petrovic, Mina, Blaukopf, Claudia, Langer, Christoph C. H., Batty, Paul, Nagaraju, Thejaswi, Doolittle, Lynda K., Rosen, Michael K., Gerlich, Daniel W.

Issue&Volume: 2022-08-03

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 cells1,2,3. Assembly of mitotic chromosomes involves DNA looping by condensin4,5,6,7,8 and chromatin compaction by global histone deacetylation9,10,11,12,13. Although condensin confers mechanical resistance to spindle pulling forces14,15,16, 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.

DOI: 10.1038/s41586-022-05027-y

Source: https://www.nature.com/articles/s41586-022-05027-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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