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The mineralocorticoid receptor (MR) is a ligand-induced transcription factor belonging to the steroid receptor family and involved in water-electrolyte homeostasis, blood pressure regulation, inflammation and fibrosis in the renocardiovascular system. The MR shares a common hormone-response-element with the glucocorticoid receptor but nevertheless elicits MR-specific effects including enhanced epidermal growth factor receptor (EGFR) expression via unknown mechanisms. The EGFR is a receptor tyrosine kinase that leads to activation of MAP kinases, but that can also function as a signal transducer for other signaling pathways. In the present study, we mechanistically investigate the interaction between a newly discovered MR- but not glucocorticoid receptor- responsive-element (=MRE1) of the EGFR promoter, specificity protein 1 (SP1) and MR to gain general insights into MR-specificity. Biological relevance of the interaction for EGFR expression and consequently for different signaling pathways in general is demonstrated in human, rat and murine vascular smooth muscle cells and cells of EGFR knockout mice. A genome-wide promoter search for identical binding regions followed by quantitative PCR validation suggests that the identified MR-SP1-MRE1 interaction might be applicable to other genes. Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.
Pubmed ID: 23821666 RIS Download
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In an effort to strongly support the collaborative nature of scientific research, BIOBASE offers access to their tools. Programs that are available through this portal are: * AliBaba 2.1: AliBaba2 is a program for predicting binding sites of transcription factor binding sites in an unknown DNA sequence. Therefore it uses the binding sites collected in TRANSFAC. AliBaba2 is currently the most specific tool for predicting sites. * Boxshade 3.3.1: Pretty Printing and Shading of Multiple-Alignment files. * ClustalW 1.8: ClustalW Multiple Sequence Alignment Program. * Dialign2.0: Multiple Sequence Alignment Program. * F-Match 1.0: F-MATCH is a program for identifying statistically overrepresented Transcription Factor Binding Sites (TFBS) in a set of sequences compared against a control set, assuming a binomial distribution of TFBS frequency. The program reads MATCH output files for the query and control sets. F-Match uses a library of mononucleotide weight matrices from TRANSFAC 6.0 * Match 1.0 Public: Match is designed for searching potential binding sites for transcription factors (TF binding sites) nucleotide sequences. MatchTM uses a library of mononucleotide weight matrices from TRANSFAC 6.0 * molwSearch 1.0: Search for transcription factors with a certain molecular weight. * P-Match 1.0: P-Match is a new tool for identifying transcription factor binding sites (TF binding sites) in DNA sequences. It combines pattern matching and weight matrix approaches thus providing higher accuracy of recognition than each of the methods alone. P-Match uses a library of mononucleotide weight matrices from TRANSFAC 6.0 along with the site alignments associated with these matrices. * Patch 1.0: Search for potential transcription factor binding sites in your own sequences with the pattern search program using TRANSFAC 6.0 public sites. * m2transfac 1.0: m2transfac is a PWM-PWM alignment interface for the TRANSFAC(R) database. For given user motifs, m2transfac reports all non-overlapping pairwise alignments to a TRANSFAC(R) matrix which satisfy a specified threshold. * MatrixCatch 2.7: The MatrixCatch tool is designed for searching potential composite elements (CEs) for transcription factors (TFs) in any DNA sequence, which may be of interest. MatrixCatch uses a library of CE matrix models, which were compiled on a basis of experimentally identified CEs collected in TRANSCOMPEL database and mononucleotide weight matrices for single TF-binding sites collected in TRANSFAC 6.0 public database. * Composite Module Analyst (CMA) 1.0: CMA reads output of Match program and applies a genetic algorithm in order to define promoter models based on the composition of transcription factor binding sites and their pairs. * PolyA Scan 0.000707: Scanning a Sequence for potential Polyadenylation Sites. * ReadSeq 2.0: ReadSeq reads and writes nucleic/protein sequences in various formats. * SignalScan: Analysis of DNA Sequences for known Eukaryotic Signals * SbBlast 1.0: Search Tool for Sequence Search in the S/MARt Binder Database. SbBlast makes use of the BLAST Sequence Similarity Search Tool - Version 2.0.13 (May-26-2000). * SnpFind 0.3: SNPFIND is a tool for searches in the Database of Single Nucleotide Polymorphisms. The search algorithm used for the database search is the BLAST algorithm. * TfBlast 0.1: Search Tool for Sequence Search in the TRANSFAC Factor Table. SbBlast makes use of the BLAST Sequence Similarity Search Tool - Version 2.0.13 (May-26-2000).
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