Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters.
Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters.
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DOI：
10.1186/1471-2164-8-459
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发表时间：
2007-12-13
期刊：
影响因子：
4.4
通讯作者：
Albà MM
中科院分区：
文献类型：
--
作者：
Bellora N;Farré D;Albà MM
基因启动子中调控基序的排列，或启动子结构，是经过数百万年的突变和选择过程的结果。在哺乳动物中，组织特异性转录调控与基因启动子中特定蛋白质相互作用DNA基序的存在有关。然而，人们对这些基序的相对位置和间距知之甚少。为了填补这一空白，我们在大量的内务管理和组织特异性基因中进行了系统的搜索，寻找在特定启动子位置显示显著偏差的基序。我们观察到驱动内务基因表达的启动子在具有强烈位置偏见的特定基序中富集，如YY1，这与驱动组织特异性表达的启动子相关性不大。我们还确定了大量的基序，这些基序在以高度组织特异性的方式表达的基因中显示位置偏差。它们包括众所周知的组织特异性基序，如肝脏、肾脏和小肠中的HNF1和HNF4基序，或睾丸中的RFX基序，以及许多潜在的新型调控基序。基于此分析，我们对小鼠基因启动子中的559个组织特异性基序进行了预测。研究表明，基序位置偏差是哺乳动物近端启动子的一个重要特征，它既影响一般基序，也影响组织特异性基序。基序位置约束根据表达宽度和组织类型定义了非常不同的启动子结构。
The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.
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