Orthology-driven mapping of bidirectional promoters in human and mouse genomes
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RESEARCH
Open Access
Orthology-driven mapping of bidirectional promoters in human and mouse genomes Mary Qu Yang1,2*, Laura Elnitski3* From 2014 International Conference on Bioinformatics and Computational Biology Las Vegas, NV, USA. 21-24 July 2014
Abstract Background: 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. Results: 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. Conclusions: 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.
Background Bidirectional promoters are the regulatory regions that fall between pairs of genes, where the 5’ ends of the genes within a pair are positioned in close proximity to one another. This spacing facilitates the initiation of transcription of both genes, creating two transcription forks that advance in opposite directions. The formal definition of a bidirectional promoter requires that the transcription * Correspondence: [email protected]; [email protected] 1 MidSouth Bioinformatics Center, Department of Information Science, George W. Donaghey College of Engineering and Information Technology, University of Arkansas at Little Rock, 2801 S. University Avenue, Little Rock, Arkansas, 72204, USA 3 National Human Genome Research Institute, National Institutes of Health, Rockville, MD 20852, USA Full list of author information is available at the end of the article
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