A minisatellite “core” element constitutes a novel, chromatin-specific activator of mts1 gene transcription

• Published in: Journal of molecular biology 1998-07, Vol.280 (2), p.227-236
• Main Authors: Prokhortchouk, Egor B, Prokhortchouk, Anna V, Rouzov, Aleksei S, Kiselev, Sergei L, Lukanidin, Eugene M, Georgiev, Georgii P
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; chromatin; Chromatin - metabolism; Conserved Sequence; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Deoxyribonuclease I - metabolism; DNA - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; DNase I hypersensitive sites; enhancer; Humans; Introns; Mice; minisatellite DNA; Minisatellite Repeats; Molecular Sequence Data; Nucleosomes - metabolism; Sequence Homology, Nucleic Acid; Trans-Activators - metabolism; transcription; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1998.1857

Expression of the mts1 gene is often associated with malignant transformation of tumor cells. Transcription of the gene is controlled by a number of positive and negative regulatory elements, all of them being localized in the first intron (+38 to +1215) of the mts1 gene. Through analysis of the distribution of DNase I hypersensitive sites in the first intron of the gene we revealed a structurally conserved region that consisted of a non-canonical NFkB binding site and a minisatellite “core” element. Deletion of the minisatellite core DNA in the context of the first intron had no effect on its regulatory capacity when assayed in transient transfections, while a fivefold decrease was observed in a pool of stably transfected cells. The minisatellite core sequence CTGGGCAGGCAG is involved in DNA-protein interactions in vivo, and is similar to a binding site for the previously identified minisatellite DNA sequence binding protein (Msbp-1). The core DNA interacted in vitro with a protein that had an apparent molecular mass of 40 kDa. These data indicate that the minisatellite DNA represents the novel, chromatin-specific element in the mts1 complex enhancer.