Institute of Pharmacology, BPC Marburg, University of Marburg, Karl-von-Frisch-Str. 1, 35043 Marburg, Germany.
School of Cellular and Molecular Medicine, Biomedical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Nat Cell Biol. 2017 Dec;19(12):1389-1399. doi: 10.1038/ncb3641. Epub 2017 Nov 13.
Re-establishment of nuclear structure and chromatin organization after cell division is integral for genome regulation or development and is frequently altered during cancer progression. The mechanisms underlying chromatin expansion in daughter cells remain largely unclear. Here, we describe the transient formation of nuclear actin filaments (F-actin) during mitotic exit. These nuclear F-actin structures assemble in daughter cell nuclei and undergo dynamic reorganization to promote nuclear protrusions and volume expansion throughout early G1 of the cell cycle. Specific inhibition of this nuclear F-actin assembly impaired nuclear expansion and chromatin decondensation after mitosis and during early mouse embryonic development. Biochemical screening for mitotic nuclear F-actin interactors identified the actin-disassembling factor cofilin-1. Optogenetic regulation of cofilin-1 revealed its critical role for controlling timing, turnover and dynamics of F-actin assembly inside daughter cell nuclei. Our findings identify a cell-cycle-specific and spatiotemporally controlled form of nuclear F-actin that reorganizes the mammalian nucleus after mitosis.
有丝分裂后核结构和染色质组织的重建对于基因组调控或发育至关重要，并且在癌症进展过程中经常发生改变。然而，子细胞中染色质扩张的机制在很大程度上仍不清楚。在这里，我们描述了有丝分裂后期核肌动蛋白丝（F-actin）的短暂形成。这些核 F-actin 结构在子细胞核中组装，并经历动态重组，以促进核突起和核体积在细胞周期的早期 G1 期扩张。对这种核 F-actin 组装的特异性抑制会损害有丝分裂后和早期小鼠胚胎发育过程中的核扩张和染色质去凝聚。有丝分裂核 F-actin 相互作用物的生化筛选鉴定了肌动蛋白解聚因子肌球蛋白 1。光遗传学调节肌球蛋白 1 揭示了其对控制子细胞核内 F-actin 组装的时间、周转率和动力学的关键作用。我们的研究结果确定了一种细胞周期特异性和时空控制的核 F-actin 形式，它在有丝分裂后重组哺乳动物核。
