Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape.
Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape.
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DOI：
10.1016/j.celrep.2013.03.014
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发表时间：
2013-04-25
期刊：
影响因子：
8.8
通讯作者：
Bulyk ML
中科院分区：
文献类型：
--
作者：
Gordân R;Shen N;Dror I;Zhou T;Horton J;Rohs R;Bulyk ML
DNA序列是转录因子（TF）与其基因组靶标的结合特异性的主要决定因素。然而，真核细胞通常同时表达具有高度相似的DNA结合基序但体内靶点不同的TF。目前，还没有很好地理解具有看似相同的DNA基序的TF如何在体内实现独特的特异性。在这里，我们使用定制的蛋白质结合微阵列来分析TF特异性的推定结合位点在其基因组序列的背景。使用酵母TF Cbf 1和Tye 7作为我们的案例研究，我们发现这些bHLH TF的结合位点（即，E-box）在体外和体内的结合不同，这取决于它们的基因组背景。计算分析表明，E-box结合位点外的核苷酸通过影响DNA结合位点的3D结构而有助于特异性。因此，局部形状的目标网站可能发挥广泛的作用，在TF家族内实现监管的特异性。
DNA sequence is a major determinant of the binding specificity of transcription factors (TFs) for their genomic targets. However, eukaryotic cells often express, at the same time, TFs with highly similar DNA binding motifs but distinct in vivo targets. Currently, it is not well understood how TFs with seemingly identical DNA motifs achieve unique specificities in vivo. Here, we used custom protein binding microarrays to analyze TF specificity for putative binding sites in their genomic sequence context. Using yeast TFs Cbf1 and Tye7 as our case study, we found that binding sites of these bHLH TFs (i.e., E-boxes) are bound differently in vitro and in vivo, depending on their genomic context. Computational analyses suggest that nucleotides outside E-box binding sites contribute to specificity by influencing the 3D structure of DNA binding sites. Thus, local shape of target sites might play a widespread role in achieving regulatory specificity within TF families.