Expression of the woodchuck N-myc2 retroposon in brain and in liver tumors is driven by a cryptic N-myc promoter

Mol Cell Biol. 1992 Dec;12(12):5336-44. doi: 10.1128/mcb.12.12.5336-5344.1992.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism*
  • Cell Line
  • DNA / metabolism
  • DNA Transposable Elements*
  • Dinucleoside Phosphates / metabolism
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, myc*
  • Humans
  • Liver Neoplasms / genetics*
  • Marmota
  • Methylation
  • Mice
  • Molecular Sequence Data
  • Organ Specificity / genetics
  • Promoter Regions, Genetic*
  • Proto-Oncogene Mas
  • Sequence Homology, Nucleic Acid
  • Terminator Regions, Genetic
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA Transposable Elements
  • Dinucleoside Phosphates
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • cytidylyl-3'-5'-guanosine
  • DNA