在缺乏特定碱基对识别的情况下的蛋白质 - DNA 结合。
Protein-DNA binding in the absence of specific base-pair recognition.
作者信息
Afek Ariel, Schipper Joshua L, Horton John, Gordân Raluca, Lukatsky David B
机构信息
Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 8410501 Israel; and.
Center for Genomic and Computational Biology, Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27708.
出版信息
Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17140-5. doi: 10.1073/pnas.1410569111. Epub 2014 Oct 13.
Until now, it has been reasonably assumed that specific base-pair recognition is the only mechanism controlling the specificity of transcription factor (TF)-DNA binding. Contrary to this assumption, here we show that nonspecific DNA sequences possessing certain repeat symmetries, when present outside of specific TF binding sites (TFBSs), statistically control TF-DNA binding preferences. We used high-throughput protein-DNA binding assays to measure the binding levels and free energies of binding for several human TFs to tens of thousands of short DNA sequences with varying repeat symmetries. Based on statistical mechanics modeling, we identify a new protein-DNA binding mechanism induced by DNA sequence symmetry in the absence of specific base-pair recognition, and experimentally demonstrate that this mechanism indeed governs protein-DNA binding preferences.
到目前为止，人们一直合理地认为，特定碱基对识别是控制转录因子（TF）与DNA结合特异性的唯一机制。与这一假设相反，我们在此表明，具有某些重复对称性的非特异性DNA序列，当存在于特定TF结合位点（TFBS）之外时，会从统计学上控制TF与DNA的结合偏好。我们使用高通量蛋白质-DNA结合测定法，来测量几种人类TF与数万个具有不同重复对称性的短DNA序列的结合水平和结合自由能。基于统计力学建模，我们确定了一种在没有特定碱基对识别的情况下由DNA序列对称性诱导的新型蛋白质-DNA结合机制，并通过实验证明该机制确实支配着蛋白质-DNA的结合偏好。
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