Genome-wide prediction and characterization of interactions between transcription factors in Saccharomyces cerevisiae.
Genome-wide prediction and characterization of interactions between transcription factors in Saccharomyces cerevisiae.
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DOI：
10.1093/nar/gkj487
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发表时间：
2006
影响因子：
14.9
通讯作者：
Qian J
中科院分区：
文献类型：
--
作者：
Yu X;Lin J;Masuda T;Esumi N;Zack DJ;Qian J
转录因子复合体的组合调控是真核生物基因调控的一个重要特征。在这里，我们提出了一种新的方法来识别转录因子（TF）之间的相互作用，依赖于它们的结合位点的关系，我们测试它使用酿酒酵母作为模型系统。该算法预测相互作用的TF对的基础上共同出现的结合基序和启动子序列中的基序之间的距离。这允许在没有已知结合基序或表达数据的情况下研究TF之间的相互作用。通过这种方法，确定了300个重要的相互作用，涉及77个TF。这些包括超过70%的已知蛋白质-蛋白质相互作用。大约一半的检测到的相互作用的基序对显示出强烈的偏好，在启动子序列中的特定的距离和方向。这些一维特征可以反映蛋白质-蛋白质相互作用的允许空间布置的约束。所观察到的特征距离的生物学相关性的证据是由以下发现提供的：具有相同特征距离的靶基因显示出比没有优选距离的靶基因显著更高的共表达。此外，所观察到的相互作用是动态的：大多数TF对不是组成型活性的，而是根据细胞的生理条件显示可变的活性。有趣的是，一些TF对活跃在多种条件下，表现出不同的距离和方向的偏好，这取决于条件。我们对TF相互作用的预测和表征可能有助于理解真核系统中的转录调控网络。
Combinatorial regulation by transcription factor complexes is an important feature of eukaryotic gene regulation. Here, we propose a new method for identification of interactions between transcription factors (TFs) that relies on the relationship of their binding sites, and we test it using Saccharomyces cerevisiae as a model system. The algorithm predicts interacting TF pairs based on the co-occurrence of their binding motifs and the distance between the motifs in promoter sequences. This allows investigation of interactions between TFs without known binding motifs or expression data. With this approach, 300 significant interactions involving 77 TFs were identified. These included more than 70% of the known protein–protein interactions. Approximately half of the detected interacting motif pairs showed strong preferences for particular distances and orientations in the promoter sequences. These one dimensional features may reflect constraints on allowable spatial arrangements for protein–protein interactions. Evidence for biological relevance of the observed characteristic distances is provided by the finding that target genes with the same characteristic distances show significantly higher co-expression than those without preferred distances. Furthermore, the observed interactions were dynamic: most of the TF pairs were not constitutively active, but rather showed variable activity depending on the physiological condition of the cells. Interestingly, some TF pairs active in multiple conditions showed preferences for different distances and orientations depending on the condition. Our prediction and characterization of TF interactions may help to understand the transcriptional regulatory networks in eukaryotic systems.