A MINISATELLITE CORE ELEMENT CONSTITUTES A NOVEL, CHROMATIN-SPECIFIC ACTIVATOR OF MTS1 GENE-TRANSCRIPTION

Expression of the mts1 gene is often associated with malignant transfo rmation of tumor cells. Transcription of the gene is controlled by a n umber 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 f irst intron of the gene we revealed a structurally conserved region th at consisted of a noncanonical 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 ass ayed in transient transfections, while a fivefold decrease was observe d in a pool of stably transfected cells. The minisatellite core sequen ce CTGGGCAGGCAG is involved in DNA-protein interactions in vivo, and i s similar to a binding site for the previously identified minisatellit e DNA sequence binding protein (Msbp1). The core DNA interacted in vit ro with a protein that had an apparent molecular mass of 40 kDa. These data indicate that the minisatellite DNA represents the novel, chroma tin-specific element in the mts1 complex enhancer. (C) 1998 Academic P ress.