What matters for lac repressor search in vivo--sliding, hopping, intersegment transfer, crowding on DNA or recognition?
What matters for lac repressor search in vivo--sliding, hopping, intersegment transfer, crowding on DNA or recognition?
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DOI：
10.1093/nar/gkv207
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发表时间：
2015-04-20
影响因子：
14.9
通讯作者：
Elf J
中科院分区：
文献类型：
--
作者：
Mahmutovic A;Berg OG;Elf J
我们已经调查了哪些方面的转录因子DNA相互作用是最重要的，以占最近在体内的搜索时间测量的二聚乳糖阻遏物。我们发现最好的协议的滑动模型，其中非特异性结合到DNA是不可能的，在第一次接触和滑动的LacI蛋白结合在高概率时，达到特定的Osym运营商。我们还发现，跳频的整体搜索速度的贡献是可以忽略不计的，虽然物理上不可避免的。给出最佳拟合的参数揭示了滑动距离，包括跳跃，接近于过去已经提出的，即约40 bp，但在非特异性DNA序列上具有出乎意料的高1D扩散常数。包括远距离DNA片段之间的片段间转移机制不会将1D扩散降低到体外值的预期分数。这表明一种机制，其中转录因子可以在体内滑动，比简单的粘度缩放参数或模型的修改所给出的更少的阻碍。例如，估计的扩散速率常数将与期望值一致，如果染色体的部分，远离算子位点，是不可访问的搜索。
We have investigated which aspects of transcription factor DNA interactions are most important to account for the recent in vivo search time measurements for the dimeric lac repressor. We find the best agreement for a sliding model where non-specific binding to DNA is improbable at first contact and the sliding LacI protein binds at high probability when reaching the specific Osym operator. We also find that the contribution of hopping to the overall search speed is negligible although physically unavoidable. The parameters that give the best fit reveal sliding distances, including hopping, close to what has been proposed in the past, i.e. ∼40 bp, but with an unexpectedly high 1D diffusion constant on non-specific DNA sequences. Including a mechanism of inter-segment transfer between distant DNA segments does not bring down the 1D diffusion to the expected fraction of the in vitro value. This suggests a mechanism where transcription factors can slide less hindered in vivo than what is given by a simple viscosity scaling argument or that a modification of the model is needed. For example, the estimated diffusion rate constant would be consistent with the expectation if parts of the chromosome, away from the operator site, were inaccessible for searching.
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