Genome-wide analysis of promoter architecture in Drosophila melanogaster
Genome-wide analysis of promoter architecture in Drosophila melanogaster
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DOI：
10.1101/gr.112466.110
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发表时间：
2011-02-01
期刊：
影响因子：
7
通讯作者：
Celniker, Susan E.
中科院分区：
文献类型：
--
作者：
Hoskins, Roger A.;Landolin, Jane M.;Celniker, Susan E.
核心启动子是高等真核生物基因调控的关键区域。然而，启动子区域的边界，在转录起始位点（TSS）分布在其中，启动子结构的功能意义的相对速率仍然知之甚少。通过整合来自三种独立和互补方法的数据，我们制作了一个高分辨率的黑腹果蝇胚胎启动子活性图谱：2100万个基因表达帽分析（CAGE）标签，120万个RNA连接酶介导的cDNA末端快速扩增（RLM-RACE）读数和50，000个帽捕获表达序列标签（EST）。我们定义了8037个基因的12，454个启动子。我们的分析表明，由于非启动子相关的RNA背景信号，以前的研究可能高估了5倍的启动子相关的CAGE簇的数量。我们发现，TSS分布形成了一个复杂的连续的形状，并在胚胎和成人中的启动子活性具有高度相似的形状在95%的情况下。这表明这些分布通常由静态元素如局部DNA序列决定，而不受动态信号如组蛋白修饰的调节。转录因子结合基序作为启动子形状的函数而差异富集，并且峰值启动子形状与基因表达的时间和空间调节相关。我们的研究结果有助于新出现的观点，即核心启动子是功能多样的，并控制模式的基因表达在果蝇和哺乳动物。
Core promoters are critical regions for gene regulation in higher eukaryotes. However, the boundaries of promoter regions, the relative rates of initiation at the transcription start sites (TSSs) distributed within them, and the functional significance of promoter architecture remain poorly understood. We produced a high-resolution map of promoters active in the Drosophila melanogaster embryo by integrating data from three independent and complementary methods: 21 million cap analysis of gene expression (CAGE) tags, 1.2 million RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE) reads, and 50,000 cap-trapped expressed sequence tags (ESTs). We defined 12,454 promoters of 8037 genes. Our analysis indicates that, due to non-promoter-associated RNA background signal, previous studies have likely overestimated the number of promoter-associated CAGE clusters by fivefold. We show that TSS distributions form a complex continuum of shapes, and that promoters active in the embryo and adult have highly similar shapes in 95% of cases. This suggests that these distributions are generally determined by static elements such as local DNA sequence and are not modulated by dynamic signals such as histone modifications. Transcription factor binding motifs are differentially enriched as a function of promoter shape, and peaked promoter shape is correlated with both temporal and spatial regulation of gene expression. Our results contribute to the emerging view that core promoters are functionally diverse and control patterning of gene expression in Drosophila and mammals.