DNA motifs in human and mouse proximal promoters predict tissue-specific expression
DNA motifs in human and mouse proximal promoters predict tissue-specific expression
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DOI：
10.1073/pnas.0508169103
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发表时间：
2006-04-18
影响因子：
11.1
通讯作者：
Zhang, MQ
中科院分区：
文献类型：
--
作者：
Smith, AD;Sumazin, P;Zhang, MQ
全面鉴定顺式调控元件是准确重建基因调控网络的必要条件。我们研究了人类和小鼠基因的近端启动子在56个终末分化组织中的差异表达。使用计算机技术来发现，评估和模拟序列元素之间的相互作用，我们系统地确定了调节模块，区分相应的转录本中的抑制表达升高。我们使用这些推定的调控模块来构建56种组织中每一种的单一预测模型。这些预测因子在80%的组织（56个中的45个）中以统计学显著性区分组织特异性表达升高与抑制表达。预测因子还揭示了顺式调控模块之间的协同作用，并解释了大规模组织特异性差异表达。对于睾丸和肝脏，预测因子包括计算预测的基序。对于大多数其他组织，预测因子揭示了实验验证的基序之间的协同作用，并指示由类似的组织特异性机制调节的基因。在近端启动子的顺式调控模块与组织特异性活性的鉴定奠定了基础，在哺乳动物基因组中的顺式调控DNA代码的完整表征和破译。
Comprehensive identification of cis-regulatory elements is necessary for accurately reconstructing gene regulatory networks. We studied proximal promoters of human and mouse genes with differential expression across 56 terminally differentiated tissues. Using in silico techniques to discover, evaluate, and model interactions among sequence elements, we systematically identified regulatory modules that distinguish elevated from inhibited expression in the corresponding transcripts. We used these putative regulatory modules to construct a single predictive model for each of the 56 tissues. These predictors distinguish tissue-specific elevated from inhibited expression with statistical significance in 80% of the tissues (45 of 56). The predictors also reveal synergy between cis-regulatory modules and explain large-scale tissue-specific differential expression. For testis and liver, the predictors include computationally predicted motifs. For most other tissues, the predictors reveal synergy between experimentally verified motifs and indicate genes that are regulated by similar tissue-specific machinery. The identification in proximal promoters of cis-regulatory modules with tissue-specific activity lays the groundwork for complete characterization and deciphering of cis-regulatory DNA code in mammalian genomes.