title: NUBIScan, an in silico approach for prediction of nuclear receptor response elements.
abstract: Nuclear receptors (NRs) are transcription factors activated by a multitude of hormones, other endogenous substances, and exogenous molecules. These proteins modulate the regulation of target genes by contacting their promoter or enhancer sequences at specific recognition sites. The identification of these response elements is the first step toward detailed insight into the regulatory mechanisms affecting a gene. We have developed NUBIScan, a computer algorithm to predict DNA recognition sites for NRs in the regulatory regions of genes. The algorithm is based on weighted nucleotide distribution matrices and combines scores from both half-sites necessary for NR dimer binding. It provides more specific identification of functional sites than previous in silico approaches, as evidenced by scanning published regulatory regions of drug-inducible genes and comparing the obtained predictions with experimental results. In prospective analyses, NUBIScan consistently identified new functional NR binding sites in sets of large sequences, which had eluded previous analyses. This is exemplified by the detailed functional analysis of the flanking region of two genes. This approach therefore facilitates the selection of likely sites of gene regulation for subsequent experimental analysis.
authors.affiliation: Division of Pharmacology/Neurobiology, Biozentrum of the University of Basel, CH-4056 Basel, Switzerland. michael.podvinec@unibas.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Podvinec
authors.forename: Michel R
authors.initials: MR
authors.lastname: Kaufmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
authors.forename: Urs A
authors.initials: UA
authors.lastname: Meyer
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000465:Algorithms; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002645:Chickens; D019295:Computational Biology / Q000379:methods*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005786:Gene Expression Regulation; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D012984:Software; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A