Abstract
BackgroundPromoters are key players in gene regulation. They receive signals from various sources (e.g. cell surface receptors) and control the level of transcription initiation, which largely determines gene expression. In vertebrates, transcription start sites and surrounding regulatory elements are often poorly defined. To support promoter analysis, we present CORG , a framework for studying upstream regions including untranslated exons (5' UTR).DescriptionThe automated annotation of promoter regions integrates information of two kinds. First, statistically significant cross-species conservation within upstream regions of orthologous genes is detected. Pairwise as well as multiple sequence comparisons are computed. Second, binding site descriptions (position-weight matrices) are employed to predict conserved regulatory elements with a novel approach. Assembled EST sequences and verified transcription start sites are incorporated to distinguish exonic from other sequences.As of now, we have included 5 species in our analysis pipeline (man, mouse, rat, fugu and zebrafish). We characterized promoter regions of 16,127 groups of orthologous genes. All data are presented in an intuitive way via our web site. Users are free to export data for single genes or access larger data sets via our DAS server . The benefits of our framework are exemplarily shown in the context of phylogenetic profiling of transcription factor binding sites and detection of microRNAs close to transcription start sites of our gene set.ConclusionThe CORG platform is a versatile tool to support analyses of gene regulation in vertebrate promoter regions. Applications for CORG cover a broad range from studying evolution of DNA binding sites and promoter constitution to the discovery of new regulatory sequence elements (e.g. microRNAs and binding sites).
Highlights
Promoters are key players in gene regulation
Detailed information about the conserved noncoding block structure are simultaneously shown for multiple upstream regions of different species
The genomic copy of the human U93 RNA is located in an intron of a series of reported spliced expressed sequence tags (ESTs); it has been verified experimentally that U93 is spliced from an intron [40]
Summary
We have improved and extended our framework of comparative analysis and annotation of vertebrate promoter regions over previous releases (see [20]). Web site offers a genomic context view (as in Figure 1) and an option to export sequence and annotation data. The CORG database is accessible via our web site. Conserved regulatory elements of different kinds (binding sites, microRNAs and UTR elements) are readily accessible to CORG users. The database is freely accessible through the website http:/ /corg.molgen.mpg.de. Steffen Grossmann annotated transcription factor binding sites and provided parts of the web interface. Andrea Tanzer analyzed known and novel RNA elements in the multiple alignments of the CORG database. Histogram of observed genomic distances between start sites of transcription and translation in man for 1,700 entries from the EPD.
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