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http://www.gene-regulation.com
Matys, V.1, Fricke, E.1, Geffers, R.1, Gößling, E.1, Hornischer, K.1, Kel-Margoulis, O. V.1, Kloos, D. U.1, Land, S.1, Michael, H.2, Münch, R.1, Reuter, I.1, Scheer, M.1, Thiele, S.1, Wingender, E.1, -1
1BIOBASE GmbH, Halchtersche Str. 33, D-38304 Wolfenbüttel, Germany
2AG Bioinformatics, GBF, German Research Centre for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany
Contact vma@biobase.de
The TRANSFAC® database (Wingender et al. 2001) has been constructed to model the interaction of eukaryotic transcription factors with their DNA-binding sites and how this affects gene expression. At its core are therefore three tables, for FACTORs, SITEs and GENEs. A link between FACTOR and SITE shows the interaction (binding) between them. Experimental evidence for this interaction is given in the SITE entry in form of the method which was used (gel shift, footprinting analysis, ...) to show the binding and the cell from which the factor was derived (factor source). On the basis of those, method and cell, a quality value is given to describe the “confidence” with which a binding activity could be assigned to a specific factor. From a collection of binding sites for a factor its DNA-binding profile (MATRIX) is derived in form of a nucleotide weight matrix. These matrices are used by the tool Match™ to find potential binding sites in uncharacterized sequences, while Patch™, another tool, uses the single sites (and IUPAC consensus sequences), which are stored in the SITE table. In the GENE table the context of the single factor-site relations within the regulatory region of a gene is given. Initially designed to link TRANSFAC® data to the TRRD and Compel databases, the GENE table has gained more and more a central role as it is not only jointly used by several of our own databases, but has been extended to one of the major links to other, external databases. As some of the regulated genes encode transcription factors themselves (which sometimes may even give rise to autoregulatory or feedback loops) there are not only links from factors via sites to target genes, but also from genes to encoded factors and vice versa. In addition to the binding properties of the transcription factors lots of information on their structure, function and tissue specificity is collected. The structure, primarily, of their DNA-binding domain is the basis for a classification of the transcription factors, shown by their assignment to a specific CLASS (Wingender 1997). While the public release is freely usable for academic research groups (http://www.gene-regulation.com), researchers from the industry are kindly asked to subscribe to the professional version with more content and extended functionality (http://www.biobase.de).
Besides a significant increase in data content, there have also been improvements in the structure of the TRANSFAC® database. With the help of the CYTOMER® database on anatomical structures and developmental stages of human and mouse the fields CP and CN on the tissue specificity of FACTORs have been started to be replaced by the better structured expression patterns (EX), giving place (organ and/or cell name), system, developmental stage, relative expression level, detection method and the detected molecule type (RNA or protein). Alongside the genomic binding sites (BS) direct links to the target genes to which these sites belong are shown as a short cut in the FACTOR table now. In the GENE table the regulating factors are also listed aside the respective binding sites (BS). For genes which code for a transcription factor links to the encoded FACTOR (FA) and from the encoded FACTOR to its GENE (GE) have been introduced. Beside this, the GENE table contains additional fields for synonyms (SY) and for chromosomal localization (CH) now, and there are references (RN, RX, RA, RT, RL) listed as well. These reference are mainly a compilation of the references dealing with the various regulatory sites, but there are also some references which are “unique” for the GENE entries. The links to TRRD and TRANSCompel™ (Compel) which were listed in separate fields formerly are listed now under database references (DR) together with new links to other external (BRENDA, LocusLink, OMIM, RefSeq) and internal databases (TRANSPATH®, PathoDB® and S/MARt DB™). Not only in the GENE, but also in the SITE and FACTOR tables the number of inter-linked databases has been increased, especially with our other databases PathoDB®, S/MARt DB™ and most importantly the TRANSPATH® database on signal transduction, allowing an integration of transcriptional regulation of the gene in the overall regulatory network of the cell.
Wingender, E., Chen, X., Fricke, E., Geffers, R., Hehl, R., Liebich, I., Krull, M., Matys, V., Michael, H., Ohnhäuser, R., Prüß, M., Schacherer, F., Thiele, S. and Urbach, S. (2001). The TRANSFAC system on gene expression regulation. Nucleic Acids Res. 29:281-283
Wingender, E. (1997) Classification scheme of eukaryotic transcription factors. Mol. Biol. 31:483-497.
Category Gene Expression
Go to the abstract in the NAR 2003 Database Issue.