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动态核形变在基因组结构重排中的作用。

Role of dynamic nuclear deformation on genomic architecture reorganization.

机构信息

Department of Mathematics, School of Science, Hiroshima University, Higashi-Hiroshima, Japan.

PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan.

出版信息

PLoS Comput Biol. 2019 Sep 11;15(9):e1007289. doi: 10.1371/journal.pcbi.1007289. eCollection 2019 Sep.

Abstract

Higher-order genomic architecture varies according to cell type and changes dramatically during differentiation. One of the remarkable examples of spatial genomic reorganization is the rod photoreceptor cell differentiation in nocturnal mammals. The inverted nuclear architecture found in adult mouse rod cells is formed through the reorganization of the conventional architecture during terminal differentiation. However, the mechanisms underlying these changes remain largely unknown. Here, we found that the dynamic deformation of nuclei via actomyosin-mediated contractility contributes to chromocenter clustering and promotes genomic architecture reorganization during differentiation by conducting an in cellulo experiment coupled with phase-field modeling. Similar patterns of dynamic deformation of the nucleus and a concomitant migration of the nuclear content were also observed in rod cells derived from the developing mouse retina. These results indicate that the common phenomenon of dynamic nuclear deformation, which accompanies dynamic cell behavior, can be a universal mechanism for spatiotemporal genomic reorganization.

摘要

高等基因组结构根据细胞类型而变化,并在分化过程中发生剧烈变化。空间基因组重排的一个显著例子是在夜间哺乳动物中的棒状光感受器细胞分化。在成年小鼠棒状细胞中发现的反转核结构是通过在终末分化过程中常规结构的重排形成的。然而,这些变化背后的机制在很大程度上仍然未知。在这里,我们通过进行细胞内实验并结合相场建模发现,通过肌动球蛋白介导的收缩导致核的动态变形有助于着丝粒聚类,并促进分化过程中的基因组结构重排。在来自发育中的小鼠视网膜的棒状细胞中也观察到核的类似的动态变形模式和核内容物的伴随迁移。这些结果表明,伴随着动态细胞行为的常见的动态核变形现象可以是时空基因组重排的通用机制。

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