Cross-species mapping of bidirectional promoters enables prediction of unannotated 5' UTRs and identification of species-specific transcripts

2Department of BiologicalSciences, Kent State University, Kent, Ohio 44242, USA.
BMC Genomics (Impact Factor: 4.04). 05/2009; 10:189. DOI: 10.1186/1471-2164-10-189
Source: PubMed

ABSTRACT Bidirectional promoters are shared regulatory regions that influence the expression of two oppositely oriented genes. This type of regulatory architecture is found more frequently than expected by chance in the human genome, yet many specifics underlying the regulatory design are unknown. Given that the function of most orthologous genes is similar across species, we hypothesized that the architecture and regulation of bidirectional promoters might also be similar across species, representing a core regulatory structure and enabling annotation of these regions in additional mammalian genomes.
By mapping the intergenic distances of genes in human, chimpanzee, bovine, murine, and rat, we show an enrichment for pairs of genes equal to or less than 1,000 bp between their adjacent 5' ends ("head-to-head") compared to pairs of genes that fall in the same orientation ("head-to-tail") or whose 3' ends are side-by-side ("tail-to-tail"). A representative set of 1,369 human bidirectional promoters was mapped to orthologous sequences in other mammals. We confirmed predictions for 5' UTRs in nine of ten manual picks in bovine based on comparison to the orthologous human promoter set and in six of seven predictions in human based on comparison to the bovine dataset. The two predictions that did not have orthology as bidirectional promoters in the other species resulted from unique events that initiated transcription in the opposite direction in only those species. We found evidence supporting the independent emergence of bidirectional promoters from the family of five RecQ helicase genes, which gained their bidirectional promoters and partner genes independently rather than through a duplication process. Furthermore, by expanding our comparisons from pairwise to multispecies analyses we developed a map representing a core set of bidirectional promoters in mammals.
We show that the orthologous positions of bidirectional promoters provide a reliable guide to directly annotate over one thousand regulatory regions in sequences of mammalian genomes, while also serving as a useful tool to predict 5' UTR positions and identify genes that are novel to a single species.

Download full-text


Available from: James M. Reecy, Jul 01, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulation of gene expression plays important role in cellular functions. With the development of sequencing techniques, more and more genomes are available and genome-wide analyses of genomic structures that may affect gene expression regulation are now possible. Analyses of several genomes have found a class of regulatory regions that contain elements that initiate transcription of two different genes positioned with a head-to-head arrangement in two opposite directions. These regulatory regions are known as bidirectional promoters. Although bidirectional promoters have been known for years, recent genome-scale studies have shown that the regulation of the expression of up to 10% of the genes are controlled by bidirectional promoters. These findings are based mostly on computational work and only a limited number of putative bidirectional promoters have been experimentally validated. Developing methods to study bidirectional promoters will allow researchers to understand how these regions are regulated and the roles that divergent transcription plays in the expression of genes. Here, we have developed a novel dual-fluorescence reporter gene vector to study the transcriptional output of bidirectional promoters. We demonstrate that this vector is capable of expressing reporter genes under the control of bidirectional promoters, using the known human OSGEP/APEX bidirectional promoter.
    Plasmid 05/2014; 74. DOI:10.1016/j.plasmid.2014.05.001 · 1.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are two well characterized cannabinoid receptors (CBRs), CB1-Rs and CB2-Rs, with other candidates, such as GPR55, PPARs and vanilloid TRPV1 (VR1) receptors, which are either activated by cannabinoids and/or endocannabinoids (eCBs). The neuronal and functional expression of CB2-Rs in the brain has been much less well characterized in comparison with the expression of the ubiquitous CB1-Rs. CB2-Rs were previously thought to be predominantly expressed in immune cells in the periphery and were traditionally referred to as peripheral CB2-Rs. We and others have now demonstrated the expression of CB2-Rs in neuronal, glial and endothelial cells in the brain, and this warrants a re-evaluation of the CNS effects of CB2-Rs. In the present review we summarize our current understanding of CNR2 genomic structure, its polymorphic nature, subtype specificity, from mice to human subjects, and its variants that confer vulnerabilities to neuropsychiatric disorders beyond neuro-immuno-cannabinoid activity.
    Journal of Psychopharmacology 03/2011; 26(1):92-103. DOI:10.1177/0269881111400652 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bidirectional transcription is an interesting feature of eukaryotic genomes; yet not all aspects of its mechanism are understood. Silkmoth choriogenesis is a model system for studying transcriptional regulation at the initiation level. As chorion genes comprise a large group of divergently transcribed gene pairs, we are presented with the possibility of investigating the intricacies of bidirectional transcription. Their well characterized 5' regulatory regions and expression profiles lay the foundation for investigating protein:protein and protein:DNA interactions, and RNA polymerase function during oocyte development. In this article we summarize current knowledge on chorion gene regulation and propose an approach to modeling bidirectional transcription using chorion promoters.
    Organogenesis 01/2010; 6(1):54-8. DOI:10.4161/org.6.1.10696 · 2.60 Impact Factor