Hughey Jacob J, Gutschow Miriam V, Bajar Bryce T, Covert Markus W
Department of Bioengineering, Stanford University, Stanford, CA 94305-4125.
Department of Bioengineering, Stanford University, Stanford, CA 94305-4125
Mol Biol Cell. 2015 Feb 1;26(3):583-90. doi: 10.1091/mbc.E14-08-1267. Epub 2014 Dec 3.
The activation dynamics of nuclear factor (NF)-κB have been shown to affect downstream gene expression. On activation, NF-κB shuttles back and forth across the nuclear envelope. Many dynamic features of this shuttling have been characterized, and most features vary significantly with respect to ligand type and concentration. Here, we report an invariant feature with regard to NF-κB dynamics in cellular populations: the distribution--the average, as well as the variance--of the time between two nuclear entries (the period). We find that this period is conserved, regardless of concentration and across several different ligands. Intriguingly, the distributions observed at the population level are not observed in individual cells over 20-h time courses. Instead, the average period of NF-κB nuclear translocation varies considerably among single cells, and the variance is much smaller within a cell than that of the population. Finally, analysis of daughter-cell pairs and isogenic populations indicates that the dynamics of the NF-κB response is heritable but diverges over multiple divisions, on the time scale of weeks to months. These observations are contrary to the existing theory of NF-κB dynamics and suggest an additional level of control that regulates the overall distribution of translocation timing at the population level.
核因子（NF）-κB的激活动力学已被证明会影响下游基因表达。激活后，NF-κB在核膜间来回穿梭。这种穿梭的许多动态特征已被表征，并且大多数特征会因配体类型和浓度的不同而有显著差异。在此，我们报告了细胞群体中NF-κB动力学的一个不变特征：两次核进入之间的时间分布——平均值以及方差（周期）。我们发现，无论浓度如何以及在几种不同配体的情况下，这个周期都是保守的。有趣的是，在群体水平观察到的分布在长达20小时的时间进程中，单个细胞中并未出现。相反，NF-κB核转位的平均周期在单个细胞之间有很大差异，并且单个细胞内的方差比群体中的方差小得多。最后，对母女细胞对和同基因群体的分析表明，NF-κB反应的动力学是可遗传的，但在数周数月的时间尺度上，经过多次分裂后会发生分化。这些观察结果与现有的NF-κB动力学理论相反，并表明存在一个额外的控制水平，可在群体水平上调节转位时间的整体分布。
