Expression of the woodchuck N-myc2 retroposon in brain and in liver tumors is driven by a cryptic N-myc promoter.
The woodchuck intronless proto-oncogene N-myc2 was initially discovered as a frequent target site for hepadnavirus integration in hepatocellular carcinoma. N-myc2 possesses characteristics of a functional retroposon derived from the woodchuck N-myc gene. We have investigated the regulatory signals governing N-myc2 expression and found that a short promoter, including a variant TATA box and potential binding sites for several transcription factors, is localized in the N-myc2 sequences homologous to the 5' untranslated region of the second N-myc exon. The corresponding region in the intron-containing woodchuck N-myc gene also exhibited promoter activity in transient transfection assays. The high evolutionary conservation of these sequences in mammalian N-myc genes suggests that they contain a cryptic N-myc promoter which may be unmasked in the particular context provided by the N-myc2 retroposon. Although N-myc2, like the woodchuck N-myc gene, contributes to an extended CpG island and was found constitutively hypomethylated, it presents a highly restricted expression pattern in adult animals. Whereas the intron-containing N-myc gene is expressed at low levels in different tissues, N-myc2 mRNA was detected only in brain tissue, raising questions about the functional significance of the maintenance of a second N-myc gene in the woodchuck genome.
Fourel
G
G
Unité de Recombinaison et Expression Génétique (Inserm U163), Institut Pasteur, Paris, France.
Transy
C
C
Tennant
B C
BC
Buendia
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004251:DNA Transposable Elements; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008392:Marmota; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D012689:Sequence Homology, Nucleic Acid; D013728:Terminator Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004247:DNA; D004251:DNA Transposable Elements; D015226:Dinucleoside Phosphates; D000090063:Proto-Oncogene Mas; C000715470:MAS1 protein, human; C015772:CpG dinucleotide