三态模型中DNA启动子的转录因子搜索
Transcription factor search for a DNA promoter in a three-states model
摘要：
为了确保快速的基因激活，转录因子（TF）使用一种称为易化扩散的机制来找到它们的DNA启动子位点。在这里，我们分析这样一个过程，TF之间的3D和1D扩散交替。在后者（TF结合到DNA）中，TF进一步在由与DNA骨架的相互作用主导的快速易位状态和其中与DNA碱基对的相互作用占主导地位的缓慢检查状态之间切换。我们推导出一个新的公式的平均搜索时间，并表明，它是更快，更不敏感的结合能波动的情况下相比，一个单一的滑动状态。我们发现，对于一个最佳的搜索，所花费的时间绑定到DNA是更大的3D时间相比，在细胞核中，与最近的实验数据。我们的研究结果进一步表明，通过TF或DNA的磷酸化或甲基化修饰开关可以有效地调节转录。
英文摘要：
To ensure fast gene activation, Transcription Factors (TF) use a mechanism known as facilitated diffusion to find their DNA promoter site. Here we analyze such a process where a TF alternates between 3D and 1D diffusion. In the latter (TF bound to the DNA), the TF further switches between a fast translocation state dominated by interaction with the DNA backbone, and a slow examination state where interaction with DNA base pairs is predominant. We derive a new formula for the mean search time, and show that it is faster and less sensitive to the binding energy fluctuations compared to the case of a single sliding state. We find that for an optimal search, the time spent bound to the DNA is larger compared to the 3D time in the nucleus, in agreement with recent experimental data. Our results further suggest that modifying switching via phosphorylation or methylation of the TF or the DNA can efficiently regulate transcription.
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