Chuang Chien-Hui, Carpenter Anne E, Fuchsova Beata, Johnson Terezina, de Lanerolle Primal, Belmont Andrew S
Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 61801, USA.
Curr Biol. 2006 Apr 18;16(8):825-31. doi: 10.1016/j.cub.2006.03.059.
Increasing evidence suggests functional compartmentalization of interphase nuclei. This includes preferential interior localization of gene-rich and early replicating chromosome regions versus peripheral localization of gene-poor and late replicating chromosome regions , association of some active genes with nuclear speckles or transcription "factories", and association of transcriptionally repressed genes with heterochromatic regions. Dynamic changes in chromosome compartmentalization imply mechanisms for long-range interphase chromatin movements. However, live cell imaging in mammalian cells has revealed limited chromatin mobility, described as "constrained diffusion". None of these studies, though, have examined a chromosome locus undergoing an inducible repositioning between two different nuclear compartments. Here we demonstrate migration of an interphase chromosome site from the nuclear periphery to the interior 1-2 hr after targeting a transcriptional activator to this site. Spot redistribution is perturbed by specific actin or nuclear myosin I mutants. Extended periods of chromosome immobility are interspersed with several minute periods in which chromosomes move unidirectionally along curvilinear paths oriented roughly perpendicular to the nuclear envelope at velocities of 0.1-0.9 microm/min over distances of 1-5 microm. Our results suggest an active mechanism for fast and directed long-range interphase chromosome movements dependent directly or indirectly on actin/myosin.
越来越多的证据表明间期细胞核存在功能分区。这包括富含基因和早期复制染色体区域优先定位于细胞核内部，而基因贫乏和晚期复制染色体区域则定位于细胞核周边，一些活跃基因与核斑点或转录“工厂”相关联，以及转录抑制基因与异染色质区域相关联。染色体分区的动态变化意味着间期染色质长距离移动的机制。然而，哺乳动物细胞的活细胞成像显示染色质的移动性有限，被描述为“受限扩散”。不过，这些研究均未检测过在两个不同核区室之间经历诱导性重新定位的染色体位点。在此，我们证明在将转录激活因子靶向该位点后1 - 2小时，一个间期染色体位点从核周边迁移至核内部。特定的肌动蛋白或核肌球蛋白I突变体扰乱了斑点的重新分布。长时间的染色体不动期间穿插着几分钟的时间段，在此期间染色体以0.1 - 0.9微米/分钟的速度沿大致垂直于核膜的曲线单向移动1 - 5微米。我们的结果表明存在一种直接或间接依赖于肌动蛋白/肌球蛋白的快速且定向的间期染色体长距离移动的活跃机制。
