Loss of lamin A function increases chromatin dynamics in the nuclear interior.
Loss of lamin A function increases chromatin dynamics in the nuclear interior.
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DOI：
10.1038/ncomms9044
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发表时间：
2015-08-24
影响因子：
16.6
通讯作者：
Garini Y
中科院分区：
文献类型：
--
作者：
Bronshtein I;Kepten E;Kanter I;Berezin S;Lindner M;Redwood AB;Mai S;Gonzalo S;Foisner R;Shav-Tal Y;Garini Y
染色质在细胞核中以高度有序而动态的方式组织，但管理这一组织的原则仍不清楚。同样，目前还不清楚各种蛋白质是否以及如何调节染色质运动，从而影响核组织。在这里，通过研究活细胞核中不同基因组区域的动力学，我们表明基因组具有高度受限的动力学。有趣的是，层蛋白A的缺失显著地改变了基因组动力学，导致从缓慢的异常扩散到快速和正常的扩散的戏剧性转变。相比之下，与层蛋白A和染色质相互作用的蛋白质LAP2α的耗尽对基因组动力学没有这样的影响。我们推测核内层粘连蛋白A形成的染色体链间相互作用有助于染色质的动态变化，并提示核内核层粘连蛋白A对染色质扩散的分子调控对维持基因组结构至关重要。核纤层介导染色质和核膜之间的相互作用，但它们也存在于整个核质中。通过测量不同基因组座位的动力学，Bronshtein等人。证明层蛋白A对于核内部的稳定性也是必需的。
Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization. Nuclear lamins mediate interactions between chromatin and the nuclear envelope, however they are also found throughout the nucleoplasm. By measuring the dynamics of different genomic loci, Bronshtein et al. show that lamin A is also required for the stability of the nuclear interior.