In vivo facilitated diffusion model.
In vivo facilitated diffusion model.
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DOI：
10.1371/journal.pone.0053956
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Metzler R
中科院分区：
文献类型：
--
作者：
Bauer M;Metzler R
在体外稀释条件下，转录因子利用促进扩散机制快速定位其靶序列。然而，这种在三维体扩散和沿DNA轮廓一维滑动之间交替的策略在拥挤的细胞内部是否仍然有益，存在高度争议。在这里，我们使用了细胞内细菌基因组的简单模型，并提出了在促进扩散框架内转录因子的体内靶标搜索的半分析模型。在不需要大量模拟的情况下，我们通过包括从实验测量中推断出的参数来确定活的大肠杆菌细胞中lac抑制因子的平均搜索时间。结果与实验结果非常一致，因此促进扩散图作为一种定量方法出现在活细菌细胞的基因调控中。此外，我们看到搜索时间对表征DNA结构的参数不是很敏感，并且细胞似乎非常接近目标定位的最佳条件。在我们的模型中，共定位机制所隐含的局部搜索只会略微加快平均搜索时间。
Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.
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