The TRANSFAC® database on transcription factors, their binding sites, nucleotide distribution matrices and regulated genes as well as the complementing database TRANSCompel® on composite elements have been further enhanced on various levels. A new web interface with different search options and integrated versions of Match™ and Patch™ provides increased functionality for TRANSFAC®. The list of databases which are linked to the common GENE table of TRANSFAC® and TRANSCompel® has been extended by: Ensembl, UniGene, EntrezGene, HumanPSD™ and TRANSPRO™. Standard gene names from HGNC, MGI and RGD, are included for human, mouse and rat genes, respectively. With the help of InterProScan, Pfam, SMART and PROSITE domains are assigned automatically to the protein sequences of the transcription factors. TRANSCompel® contains now, in addition to the COMPEL table, a separate table for detailed information on the experimental EVIDENCE on which the composite elements are based. Finally, for TRANSFAC®, in respect of data growth, in particular the gain of Drosophila transcription factor binding sites (by courtesy of the Drosophila DNase I footprint database) and of Arabidopsis factors (by courtesy of DATF, Database of Arabidopsis Transcription Factors) has to be stressed. The here described public releases, TRANSFAC® 7.0 and TRANSCompel® 7.0, are accessible under .

The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.

Match is a weight matrix-based tool for searching putative transcription factor binding sites in DNA sequences. Match is closely interconnected and distributed together with the TRANSFAC database. In particular, Match uses the matrix library collected in TRANSFAC and therefore provides the possibility to search for a great variety of different transcription factor binding sites. Several sets of optimised matrix cut-off values are built in the system to provide a variety of search modes of different stringency. The user may construct and save his/her specific user profiles which are selected subsets of matrices including default or user-defined cut-off values. Furthermore a number of tissue-specific profiles are provided that were compiled by the TRANSFAC team. A public version of the Match tool is available at: http://www.gene-regulation.com/pub/programs.html#match. The same program with a different web interface can be found at http://compel.bionet.nsc.ru/Match/Match.html. An advanced version of the tool called Match Professional is available at http://www.biobase.de.

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TRANSPATH® is a database about signal transduction events. It provides information about signaling molecules, their reactions and the pathways these reactions constitute. The representation of signaling molecules is organized in a number of orthogonal hierarchies reflecting the classification of the molecules, their species-specific or generic features, and their post-translational modifications. Reactions are similarly hierarchically organized in a three-layer architecture, differentiating between reactions that are evidenced by individual publications, generalizations of these reactions to construct species-independent ‘reference pathways’ and the ‘semantic projections’ of these pathways. A number of search and browse options allow easy access to the database contents, which can be visualized with the tool PathwayBuilder™. The module PathoSign adds data about pathologically relevant mutations in signaling components, including their genotypes and phenotypes. TRANSPATH® and PathoSign can be used as encyclopaedia, in the educational process, for vizualization and modeling of signal transduction networks and for the analysis of gene expression data. TRANSPATH® Public 6.0 is freely accessible for users from non-profit organizations under .

Loss of intestinal mucosa integrity is an important factor in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to characterize expression changes and allelic variants of genes related to intestinal epithelial barrier function in this disease. Therefore, ileal and colonic mucosal biopsies from nonaffected regions of patients with ulcerative colitis (UC) and Crohn's disease (CD), as well as non-IBD probands, were subjected to Affymetrix DNA-microarray analysis. Real-time reverse transcription polymerase chain reaction was used for verification in larger IBD sample numbers. Disturbed mRNA expression was identified for several mucin genes in both disease groups and tissues. A significant downregulation in the colon was obtained for MUC2 in CD and MUC12 in CD and UC. Expression analysis of all dysregulated mucins in a broad human tissue panel revealed dominant epithelial tissue-specific transcription. In silico analysis of the regulatory regions of these mucins indicated nuclear factor kappaB (NFkappaB) binding sites in each promoter. Furthermore, NFkappaB was overrepresented in mucin promoters and a component of a specific combination of transcription factors (composite module). In vivo stimulation experiments in the adenocarcinoma cell line LS174T showed inducible mucin expression by the cytokines tumor necrosis factor-alpha and transforming growth factor-beta, which could be blocked by NFkappaB signaling inhibitors. Allelic discrimination screening obtained statistically significant associations for the MUC2-V116M (P = 0.003) polymorphism with CD and for MUC4-A585S (P = 0.025), as well as MUC13-R502S (P = 0.0003) with UC. These data suggest that the disturbed expression of mucin genes and the connection to the NFkappaB pathway may influence the integrity of the intestine and therefore contribute to the pathophysiology of IBD.

Background: Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments.

Originating from COMPEL, the TRANSCompel database emphasizes the key role of specific interactions between transcription factors binding to their target sites providing specific features of gene regulation in a particular cellular content. Composite regulatory elements contain two closely situated binding sites for distinct transcription factors and represent minimal functional units providing combinatorial transcriptional regulation. Both specific factor--DNA and factor--factor interactions contribute to the function of composite elements (CEs). Information about the structure of known CEs and specific gene regulation achieved through such CEs appears to be extremely useful for promoter prediction, for gene function prediction and for applied gene engineering as well. Each database entry corresponds to an individual CE within a particular gene and contains information about two binding sites, two corresponding transcription factors and experiments confirming cooperative action between transcription factors. The COMPEL database, equipped with the search and browse tools, is available at http://www.gene-regulation.com/pub/databases.html#transcompel. Moreover, we have developed the program CATCH for searching potential CEs in DNA sequences. It is freely available as CompelPatternSearch at http://compel.bionet.nsc.ru/FunSite/CompelPatternSearch.html.