Orthology-driven mapping of bidirectional promoters in human and mouse genomes.
Orthology-driven mapping of bidirectional promoters in human and mouse genomes.
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DOI：
10.1186/1471-2105-15-s17-s1
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发表时间：
2014
影响因子：
3
通讯作者：
Elnitski L
中科院分区：
文献类型：
--
作者：
Yang M;Elnitski L
在所有脊椎动物物种中存在双向启动子，表明启动子可以保持在直位。因此，这种类型的启动子跨物种的全面的正交定位的鉴定可以促进控制双向基因表达的调控机制的阐明。然而，基因组中许多转录区域缺乏注释可能影响这些启动子的直系命名。人类和小鼠的基因组已经相对较好地注释。因此，我们使用它们作为模型来研究双向启动子的直系同源模式。我们开发了一种方法来注释这些调控区域，通过确认在启动子的每一侧发现的基因的同源性。在这篇手稿中，我们报告了人类和小鼠基因组之间的跨物种比较，其中双向启动子集调节UCSC已知基因和剪接的EST注释从人类映射到小鼠，反之亦然。我们通过在第二个物种中存在的邻位侧翼基因注释来验证数百个邻位双向启动子。我们还表明，这些orthopathy启动子的调节活性赋予类似的基因表达谱在21个组织中的人类和小鼠。特别地，超过三分之一的从剪接EST注释注释的人双向启动子调节ncRNA，其中超过90%是lncRNA。虽然进化保守性在启动子中显示出比编码区更弱的签名，但我们的正交基因定位技术表明，大多数双向启动子排列在人类和小鼠基因组中是保守的，这表明了一种关键功能。此外，类似的表达模式的orthopathy基因集表明，在很大程度上仍然保守的调控机制。
The presence of bidirectional promoters in all vertebrate species suggests that the promoters may be maintained in orthologous positions. Therefore the identification of the comprehensive orthologous mapping of this type promoter across species can facilitate elucidation of regulatory mechanisms controlling bidirectional gene expression. However, the lack of annotation for many transcribed regions in the genome can impact the orthology designation of these promoters. Human and mouse are among genomes that have been relatively well annotated. Thus we used them as models to study the orthologous patterns of bidirectional promoters. We developed a method to annotate these regulatory regions by confirming the orthology of the genes found on each side of the promoters. In this manuscript we report the cross-species comparisons between human and mouse genomes, where the bidirectional promoter sets regulating UCSC Known Genes and spliced EST annotations were mapped from human to mouse and vice versa. We validate hundreds of orthologous bidirectional promoters through the presence of orthologous flanking gene annotations in the second species. We also show that regulatory activity of these orthologous promoters confers similar gene expression profiles in 21 tissues of human and mouse. In particular, more than one third of human bidirectional promoters annotated from spliced EST annotations regulate ncRNA, of which over 90% are lncRNAs. Although evolutionary conservation shows a weaker signature in promoters than coding regions, our technique of mapping of orthologous genes shows that most bidirectional promoter arrangements are conserved across human and mouse genomes, suggesting a critical function. In addition, the similar expression patterns of the orthologous gene sets indicate that the regulatory mechanisms remain largely conserved as well.