DNA序列相关性影响非特异性转录因子-DNA结合亲和力
DNA sequence correlations shape nonspecific transcription factor-DNA binding affinity
摘要：
转录因子（TF）是在基因组的启动子区域结合DNA并且促进或抑制基因表达的调节蛋白。在这里，我们预测分析，增强同源寡核苷酸序列的相关性，如聚（dA：dT）和聚（dC：dG）束，统计学上增强非特异性TF-DNA结合亲和力。这种预测是通用的和定性的模型的微观参数无关。我们发现，非特异性TF结合亲和力普遍控制的强度和对称性的DNA序列相关性。我们进行相关性分析的酵母基因组，并表明，DNA区域高度占据TF表现出更强的同源寡核苷酸序列的相关性，从而更高的非特异性结合的倾向，相比，占用区域。我们认为，这种效应起到了一个有效的本地化潜力的作用，提高准一维扩散的TF在DNA附近，加快随机搜索过程中的特定TF结合位点。预测的效果也强加了TF-DNA结合基序的大小上界。
英文摘要：
Transcription factors (TFs) are regulatory proteins that bind DNA in promoter regions of the genome and either promote or repress gene expression. Here we predict analytically that enhanced homo-oligonucleotide sequence correlations, such as poly(dA:dT) and poly(dC:dG) tracts, statistically enhance non-specific TF-DNA binding affinity. This prediction is generic and qualitatively independent of microscopic parameters of the model. We show that non-specific TF binding affinity is universally controlled by the strength and symmetry of DNA sequence correlations. We perform correlation analysis of the yeast genome and show that DNA regions highly occupied by TFs exhibit stronger homo-oligonucleotide sequence correlations, and thus higher propensity for non-specific binding, as compared with poorly occupied regions. We suggest that this effect plays the role of an effective localization potential enhancing the quasi-one-dimensional diffusion of TFs in the vicinity of DNA, speeding up the stochastic search process for specific TF binding sites. The predicted effect also imposes an upper bound on the size of TF-DNA binding motifs.
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