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有丝分裂染色体与核质比和细胞大小成比例。

Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in .

机构信息

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

Department of Systems Biology, University of Massachusetts Medical School, Worcester, United States.

出版信息

Elife. 2023 Apr 25;12:e84360. doi: 10.7554/eLife.84360.

Abstract

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to scale coordinately with mitotic spindles, but the underlying mechanisms are unclear. Here we combine in vivo and in vitro approaches using eggs and embryos from the frog to show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle, and nuclear size in vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be reset by cytoplasmic factors from earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin α scales mitotic chromosomes to cell surface area/volume ratio (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and Hi-C data suggest that mitotic chromosomes shrink during embryogenesis through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter chromosome axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.

摘要

在早期胚胎发生的快速和还原分裂过程中,亚细胞结构如核和有丝分裂纺锤体按比例缩小到细胞尺寸减小。有丝分裂染色体在发育过程中也会缩小,大概是为了与有丝分裂纺锤体协调缩放,但潜在的机制尚不清楚。在这里,我们结合了使用青蛙的卵和胚胎的体内和体外方法,表明有丝分裂染色体的缩放在机制上与其他形式的亚细胞缩放不同。我们发现有丝分裂染色体在体内与细胞、纺锤体和核大小连续缩放。然而,与纺锤体和核不同的是,细胞质因子不能从早期发育阶段重新设置有丝分裂染色体的大小。在体外,增加核质比(N/C)足以通过有丝分裂间期母源性因子的差异加载来重现有丝分裂染色体的缩放,但不能重现核或纺锤体的缩放。另一个途径涉及输入蛋白α(importin α),它在中期通过与细胞表面积/体积比(SA/V)的差异结合来调节有丝分裂染色体的大小。最后,单个染色体免疫荧光和 Hi-C 数据表明,有丝分裂染色体在胚胎发生过程中通过减少凝聚素 I 的募集而缩小,导致 DNA 环结构的重大重排,以适应在更短的染色体轴上的相同量的 DNA。总之,我们的研究结果表明,有丝分裂染色体的大小是如何通过早期胚胎中空间和时间上不同的发育线索来设定的。

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