A minisatellite "core" element constitutes a novel, chromatin-specific activator of mts1 gene transcription.
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.
Prokhortchouk
E B
EB
Laboratory of Molecular Cancer Genetics, Institute of Gene Biology, Vavilova 34/5, Moscow, 117334, Russia.
Prokhortchouk
A V
AV
Rouzov
A S
AS
Kiselev
S L
SL
Lukanidin
E M
EM
Georgiev
G P
GP
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000378:metabolism*; D017124:Conserved Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D006801:Humans; D007438:Introns; D051379:Mice; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D002843:Chromatin; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D015534:Trans-Activators; D004247:DNA; D003850:Deoxyribonuclease I