Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences
Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences
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DOI：
10.1016/j.cell.2008.05.024
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发表时间：
2008-06-27
期刊：
影响因子：
64.5
通讯作者：
Hughes, Timothy R.
中科院分区：
文献类型：
--
作者：
Berger, Michael F.;Badis, Gwenael;Hughes, Timothy R.
大多数同源结构域在基因组内是独特的，但许多同源结构域在广泛的进化距离上是高度保守的，这意味着它们精确的DNA结合特异性的强选择。我们确定了大多数（168）小鼠同源结构域的所有可能的8碱基序列的结合偏好，揭示了丰富和复杂的序列特异性模式，并显示至少有65个不同的同源结构域DNA结合活性。我们开发了一个计算系统，成功地预测了同源结构域蛋白质的结合位点，远至果蝇和C。elegans，我们推断出大多数已知动物同源结构域的完整8-mer结合谱。我们的研究结果提供了一个前所未有的分辨率在这个简单的域结构的分析，并建议在序列识别的变化可能是其功能多样性和进化成功的一个因素。
Most homeodomains are unique within a genome, yet many are highly conserved across vast evolutionary distances, implying strong selection on their precise DNA-binding specificities. We determined the binding preferences of the majority (168) of mouse homeodomains to all possible 8-base sequences, revealing rich and complex patterns of sequence specificity and showing that there are at least 65 distinct homeodomain DNA-binding activities. We developed a computational system that successfully predicts binding sites for homeodomain proteins as distant from mouse as Drosophila and C. elegans, and we infer full 8-mer binding profiles for the majority of known animal homeodomains. Our results provide an unprecedented level of resolution in the analysis of this simple domain structure and suggest that variation in sequence recognition may be a factor in its functional diversity and evolutionary success.