Transcriptional regulation of the N-myc gene: identification of positive regulatory element and its double- and single-stranded DNA binding proteins.
The N-myc gene is amplified and overexpressed in neuroblastoma, retinoblastoma and small cell lung carcinoma, and is considered to be related to cell proliferation and/or differentiation. The transcriptional regulatory sequences of the c-myc gene have been already identified, while those of N-myc have remained obscure for a long time. In this report, we have identified several positive and negative transcriptional regulatory elements in the upstream region of the mouse N-myc gene. Among them, an activating sequence spanning -860 to -797 bp (63 bp) could be reduced to a functional core of 21 bp from -846 to -826. This sequence, termed N21 box, worked as a positive transcriptional element when linked directly upstream (but not downstream) of the putative N-myc promoter in HeLa, not in IMR32 cells. At least two proteins, of 42 kDa and 100 kDa, bound to the double-stranded N21 box, and were expressed in HeLa as well as in IMR32 cells. Moreover, the plus strand of N21 box could be specifically bound by a species of 42 kDa from either cell type and by a 37 kDa protein found only in HeLa cells. These proteins may be factors binding to positive transcriptional regulatory elements and may have a role in the regulation of N-myc expression.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Nakagawa
T
T
Iguchi-Ariga
S M
SM
Ariga
H
H
D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D015500:Chloramphenicol O-Acetyltransferase