Cross-species mapping of bidirectional promoters enables prediction of unannotated 5' UTRs and identification of species-specific transcripts
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.
Full-textDOI: · Available from: James M. Reecy, May 05, 2015
SourceAvailable from: Cédric Meersseman[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; DOI:10.1016/j.plasmid.2014.05.001 · 1.76 Impact Factor
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ABSTRACT: The mammalian genome is extensively transcribed, a large fraction of which is divergent transcription from promoters and enhancers that is tightly coupled with active gene transcription. Here, we propose that divergent transcription may shape the evolution of the genome by new gene origination.Cell 11/2013; 155(5):990-996. DOI:10.1016/j.cell.2013.10.048 · 33.12 Impact Factor
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ABSTRACT: Differential regulation at the level of transcription provides a means for controlling gene expression in eukaryotes, especially during development. Insect model systems have been extensively used to decipher the molecular basis of such regulatory cascades, and one of the oldest such model systems is the regulation of chorion gene expression during ovarian follicle maturation. Recent experimental and technological advances have shed new light onto the system, allowing us to revisit it. Thus, in this review we try to summarize almost 40 years' worth of studies on chorion gene regulation while-by comparing Bombyx mori and Drosophila melanogaster models-attempting to present a comprehensive, unified model of the various regulatory aspects of choriogenesis that takes into account the evolutionary conservation and divergence of the underlying mechanisms. Expected final online publication date for the Annual Review of Entomology Volume 60 is January 07, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.Annual Review of Entomology 10/2014; 60(1). DOI:10.1146/annurev-ento-010814-020810 · 13.02 Impact Factor