Comparative promoter region analysis powered by CORG.
BACKGROUND
Promoters 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 http://corg.molgen.mpg.de, a framework for studying upstream regions including untranslated exons (5' UTR).


METHODS
The 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 http://tomcat.molgen.mpg.de:8080/das. 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.


CONCLUSIONS
The 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).
Dieterich
Christoph
C
Computational Molecular Biology Department, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany. christoph.dieterich@molgen.mpg.de
Grossmann
Steffen
S
Tanzer
Andrea
A
Röpcke
Stefan
S
Arndt
Peter F
PF
Stadler
Peter F
PF
Vingron
Martin
M
D020121:5' Untranslated Regions; D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D005091:Exons; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D016678:Genome; D006801:Humans; D020407:Internet; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D012984:Software; D013045:Species Specificity; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic; D015027:Zebrafish
D020121:5' Untranslated Regions; D035683:MicroRNAs; D014157:Transcription Factors; D012313:RNA
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