Cell type-specific activity of the N-myc promoter in human neuroblastoma cells is mediated by a downstream silencer

K. A. Woodruff, J. D. Rosenblatt, T. B. Moore, R. H. Medzoyan, D. S.M. Pai, J. L. Noland, J. M. Yamashiro, R. K. Wada

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The N-myc oncogene is actively transcribed in many neuroblastoma tumors, but is not expressed in mature, normal tissue of any type. Chloramphenicol acetyl transferase (CAT) assays of constructs containing N-myc sequence transfected into N-myc expressing LA-N-5 neuroblastoma cells or non-expressing HeLa carcinoma cells have revealed a 201 base pair (bp) regulatory region mediating the cell type-specific activity of the promoter. While located downstream from 5' mRNA cap sites, the region appears to function by preventing transcriptional initiation. This downstream region is capable of suppressing promoter activity independently of position, and contains an element having 100% homology with the 9 bp consensus sequence of a transcriptional silencer found in the upstream region of the lysozyme gene. DNA gel retardation assays have shown that this sequence is involved in a specific DNA-protein interaction with nuclear extract from HeLa cells that is distinct from that occurring with extract from LA-N-5 cells. These results suggest that the N-myc promoter's cell type-specific activity is regulated by a downstream silencer, and that differential binding of regulatory protein from that present in non-expressing cells may result in the constitutive N-myc expression seen in neuroblastoma.

Original languageEnglish (US)
Pages (from-to)1335-1341
Number of pages7
JournalOncogene
Volume10
Issue number7
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • Downstream silencer
  • N-myc
  • Neuroblastoma

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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