Genome-wide analysis of core promoter elements from conserved human and mouse orthologous pairs.
Genome-wide analysis of core promoter elements from conserved human and mouse orthologous pairs.
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DOI：
10.1186/1471-2105-7-114
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发表时间：
2006-03-07
影响因子：
3
通讯作者：
Davuluri RV
中科院分区：
文献类型：
--
作者：
Jin VX;Singer GA;Agosto-Pérez FJ;Liyanarachchi S;Davuluri RV
典型的核心启动子元件包括TATA盒、启动子（Inr）、下游核心启动子元件（DPE）、TFIIB识别元件（BRE）和新发现的motif 10元件（MTE）。这些核心启动子元件的基序是高度简并的，当试图在启动子序列中检测它们时，往往会导致很高的错误发现率。在这项研究中，我们首次对具有实验支持的转录起始位点的同源小鼠和人类启动子中的这些核心启动子元件进行了分析。我们使用位置权重矩阵（PWMs）和同源小鼠和人类序列的保守程度的组合来识别这些不同的元素，这一过程显著降低了基序发现的假阳性率。通过对9010对同源小鼠-人启动子对的分析，我们发现了两种三方协同效应组合：TATA-Inr-MTE和BRE-Inr-MTE。前者先前已在人类中被推定确定，但后者代表了一种新的协同关系。我们的研究结果表明，DNA序列保守可以极大地提高人类基因组中功能性核心启动子元件的鉴定。数据还强调了两个或多个核心启动子元素协同发生的重要性。此外，本文提供的序列数据和结果可以帮助建立更好的计算模型来预测启动子区域的转录起始位点，这仍然是最具挑战性的问题之一。
The canonical core promoter elements consist of the TATA box, initiator (Inr), downstream core promoter element (DPE), TFIIB recognition element (BRE) and the newly-discovered motif 10 element (MTE). The motifs for these core promoter elements are highly degenerate, which tends to lead to a high false discovery rate when attempting to detect them in promoter sequences. In this study, we have performed the first analysis of these core promoter elements in orthologous mouse and human promoters with experimentally-supported transcription start sites. We have identified these various elements using a combination of positional weight matrices (PWMs) and the degree of conservation of orthologous mouse and human sequences – a procedure that significantly reduces the false positive rate of motif discovery. Our analysis of 9,010 orthologous mouse-human promoter pairs revealed two combinations of three-way synergistic effects, TATA-Inr-MTE and BRE-Inr-MTE. The former has previously been putatively identified in human, but the latter represents a novel synergistic relationship. Our results demonstrate that DNA sequence conservation can greatly improve the identification of functional core promoter elements in the human genome. The data also underscores the importance of synergistic occurrence of two or more core promoter elements. Furthermore, the sequence data and results presented here can help build better computational models for predicting the transcription start sites in the promoter regions, which remains one of the most challenging problems.
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