Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues.
Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues.
复制标题
DOI：
10.1093/nar/gkl595
复制
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;Zack DJ;Qian J
组织特异性基因的表达通常受不止一个转录因子（TF）的调控。多个TF协同工作以实现组织特异性。为了探索这些复杂的TF相互作用网络，我们对30种人体组织的TF相互作用进行了大规模分析。我们首先根据基因表达数据库确定了30种组织的组织特异性基因。然后，我们评估的相对位置和组织特异性基因的启动子中的结合位点的共存的TF之间的关系。预测的TF-TF相互作用通过已知的蛋白质-蛋白质相互作用和其靶基因的共表达来验证。我们发现，我们的预测富含已知的蛋白质-蛋白质相互作用（>随机预期的80倍）。此外，我们发现靶基因在感兴趣的组织中显示出最高的共表达。我们的研究结果表明，非组织特异性转录因子在组织特异性基因的调控中发挥着重要作用。此外，他们还表明，单个TF可以通过与不同的TF伴侣相互作用来促进不同组织中的组织特异性。最后，我们确定了几个组织特异性TF簇，可能在组织特异性基因调控中发挥重要作用。
Tissue-specific gene expression is generally regulated by more than a single transcription factor (TF). Multiple TFs work in concert to achieve tissue specificity. In order to explore these complex TF interaction networks, we performed a large-scale analysis of TF interactions for 30 human tissues. We first identified tissue-specific genes for 30 tissues based on gene expression databases. We then evaluated the relationships between TFs using the relative position and co-occurrence of their binding sites in the promoters of tissue-specific genes. The predicted TF–TF interactions were validated by both known protein–protein interactions and co-expression of their target genes. We found that our predictions are enriched in known protein–protein interactions (>80 times that of random expectation). In addition, we found that the target genes show the highest co-expression in the tissue of interest. Our findings demonstrate that non-tissue specific TFs play a large role in regulation of tissue-specific genes. Furthermore, they show that individual TFs can contribute to tissue specificity in different tissues by interacting with distinct TF partners. Lastly, we identified several tissue-specific TF clusters that may play important roles in tissue-specific gene regulation.