Motif composition, conservation and condition-specificity of single and alternative transcription start sites in the Drosophila genome
Motif composition, conservation and condition-specificity of single and alternative transcription start sites in the Drosophila genome
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DOI：
10.1186/gb-2009-10-7-r73
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发表时间：
2009-01-01
期刊：
影响因子：
12.3
通讯作者：
Ohler, Uwe
中科院分区：
文献类型：
--
作者：
Rach, Elizabeth A.;Yuan, Hsiang-Yu;Ohler, Uwe
背景：转录启动是基因表达调控的关键组成部分。MRNA5‘全长测序技术增强了我们对哺乳动物转录起始点(TSS)的理解，揭示了基因组水平上不同的起始模式。结果：为了识别果蝇中的TSS，我们对现有的5’表达序列标签(EST)进行了系统聚类，得到了约4000个基因的5665个TSS的高质量集合。我们区分了两种启动模式：‘峰值’TSS和‘广泛’TSS簇群。峰值启动子被发现包含位置特定的序列元件；相反，广泛的启动子与非位置特定的元件相关联。在其他果蝇基因组的比对中，序列元件在黑腹果蝇亚群中的保守性水平超过90%，但在远端物种中显著下降。广谱启动子中的元素保守性比峰值启动子中的低。在描述EST的分布时，TSS的%表现出与八种不同时空条件中的一种的明显关联。现有的全基因组平铺阵列时间序列数据显示，在具有不同替代启动子的大多数基因上，胚胎活动的不同时间模式。许多具有母系遗传转录本的基因被发现在发育后期使用了替代启动子。与合子活性启动子相比，母系遗传转录本的核心启动子在基序组成上存在差异。结论：我们的研究提供了果蝇TSSS的全面图谱以及它们的利用条件。基序与启动模式和时空利用的明显差异说明了转录启动的复杂调控密码。
Background: Transcription initiation is a key component in the regulation of gene expression. mRNA 5' full-length sequencing techniques have enhanced our understanding of mammalian transcription start sites (TSSs), revealing different initiation patterns on a genomic scale.Results: To identify TSSs in Drosophila melanogaster, we applied a hierarchical clustering strategy on available 5' expressed sequence tags (ESTs) and identified a high quality set of 5,665 TSSs for approximately 4,000 genes. We distinguished two initiation patterns: 'peaked' TSSs, and 'broad' TSS cluster groups. Peaked promoters were found to contain location-specific sequence elements; conversely, broad promoters were associated with non-location-specific elements. In alignments across other Drosophila genomes, conservation levels of sequence elements exceeded 90% within the melanogaster subgroup, but dropped considerably for distal species. Elements in broad promoters had lower levels of conservation than those in peaked promoters. When characterizing the distributions of ESTs, 64% of TSSs showed distinct associations to one out of eight different spatiotemporal conditions. Available whole-genome tiling array time series data revealed different temporal patterns of embryonic activity across the majority of genes with distinct alternative promoters. Many genes with maternally inherited transcripts were found to have alternative promoters utilized later in development. Core promoters of maternally inherited transcripts showed differences in motif composition compared to zygotically active promoters.Conclusions: Our study provides a comprehensive map of Drosophila TSSs and the conditions under which they are utilized. Distinct differences in motif associations with initiation pattern and spatiotemporal utilization illustrate the complex regulatory code of transcription initiation.