An integrated model of transcription factor diffusion shows the importance of intersegmental transfer and quaternary protein structure for target site finding.
An integrated model of transcription factor diffusion shows the importance of intersegmental transfer and quaternary protein structure for target site finding.
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DOI：
10.1371/journal.pone.0108575
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lipkow K
中科院分区：
文献类型：
--
作者：
Schmidt HG;Sewitz S;Andrews SS;Lipkow K
我们提出了一个转录因子运动的计算模型，该模型解释了观察到的转录因子的快速靶标发现，以及这种运动如何影响蛋白质和基因组结构。使用Smoldyn软件，我们模拟了转录因子的运动，这些运动是由核质中不受限制的3D扩散、沿着DNA细丝滑动以及通过节间转移在细丝之间直接转移而产生的。这展示了转录因子找到目标的方式的细粒度图像，比仅3D扩散所允许的速度快两个数量级。真核生物基因组在启动子周围包含一段核小体自由区(NFR)；我们的模型表明，这些NFR的存在和大小可以解释为它们作为触角，转录因子在触角上滑动以到达它们的靶标。此外，我们的模型表明，片段间转移可能塑造了转录因子的四级结构：序列特异性DNA结合蛋白异常地富含二聚体和四聚体，可能是因为它们允许片段间转移，从而加速了靶点的寻找。最后，我们的模型表明，在小范围的3D扩散中可以出现跳跃运动。这解释了在体外观察到的一些DNA结合蛋白明显较长的滑动长度。总之，这些结果表明，转录因子扩散动力学有助于推动蛋白质和基因组结构的进化。
We present a computational model of transcription factor motion that explains both the observed rapid target finding of transcription factors, and how this motion influences protein and genome structure. Using the Smoldyn software, we modelled transcription factor motion arising from a combination of unrestricted 3D diffusion in the nucleoplasm, sliding along the DNA filament, and transferring directly between filament sections by intersegmental transfer. This presents a fine-grain picture of the way in which transcription factors find their targets two orders of magnitude faster than 3D diffusion alone allows. Eukaryotic genomes contain sections of nucleosome free regions (NFRs) around the promoters; our model shows that the presence and size of these NFRs can be explained as their acting as antennas on which transcription factors slide to reach their targets. Additionally, our model shows that intersegmental transfer may have shaped the quaternary structure of transcription factors: sequence specific DNA binding proteins are unusually enriched in dimers and tetramers, perhaps because these allow intersegmental transfer, which accelerates target site finding. Finally, our model shows that a ‘hopping’ motion can emerge from 3D diffusion on small scales. This explains the apparently long sliding lengths that have been observed for some DNA binding proteins observed in vitro. Together, these results suggest that transcription factor diffusion dynamics help drive the evolution of protein and genome structure.
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影响因子：
3.7
作者：
Dross N;Spriet C;Zwerger M;Müller G;Waldeck W;Langowski J
通讯作者：
Langowski J
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
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Li KC
影响因子：
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作者：
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通讯作者：
Iwahara J
DOI：
10.1073/pnas.0805050105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Doucleff, Michaeleen;Clore, G. Marius
通讯作者：
Clore, G. Marius