Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors
Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors
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DOI：
10.1093/nar/30.5.1255
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发表时间：
2002-03-01
影响因子：
14.9
通讯作者：
Church, GM
中科院分区：
文献类型：
--
作者：
Bulyk, ML;Johnson, PLF;Church, GM
我们可以使用微阵列结合实验来确定许多可能的序列变化在转录因子结合位点中的影响。分析野生型和突变体ZIF263（EGR1）的锌手指与三胞胎结合位点包含所有可能的中心3的微阵列结合的锌手指表明，转录因子结合位点的核苷酸不能独立处理。这表明当前表征转录因子结合位点的实践通过突变结合位点的单个位置在石灰下一个基对并不能提供序列特异性的真实情况。同样，当前使用共识序列的生物信息学实践，甚至是单核苷酸频率重量矩阵，以提供更完整的转录因子结合位点的描述，在描述真正结合位点特异性方面并不准确，因为这些方法依赖于核苷酸的假设。结合位点对结合亲和力产生独立的影响。我们的结果强调了所有可能结合位点的完整参考表对于比较各种DNA序列的蛋白质结合偏好的重要性。我们还显示了结果表明，使用所有可能结合位点的特定子集的微阵列结合数据可用于推断所有可能的全长结合位点的相对结合亲和力，鉴于已知的结合位点，用于用作现场偏好细化的起始序列。
We can determine the effects of many possible sequence variations in transcription factor binding sites using microarray binding experiments. Analysis of wild-type and mutant Zif263 (Egr1) zinc fingers bound to microarrays containing all possible central 3 by triplet binding sites indicates that the nucleotides of transcription factor binding sites cannot be treated independently. This indicates that the current practice of characterizing transcription factor binding sites by mutating individual positions of binding sites one base pair at a lime does not provide a true picture of the sequence specificity. Similarly, current bioinformatic practices using either just a consensus sequence, or even mononucleotide frequency weight matrices to provide more complete descriptions of transcription factor binding sites, are not accurate in depicting the true binding site specificities, since these methods rely upon the assumption that the nucleotides of binding sites exert independent effects on binding affinity. Our results stress the importance of complete reference tables of all possible binding sites for comparing protein binding preferences for various DNA sequences. We also show results suggesting that microarray binding data using particular subsets of all possible binding sites can be used to extrapolate the relative binding affinities of all possible full-length binding sites, given a known binding site for use as a starting sequence for site preference refinement.