Structure and autoregulation of the c-rel promoter

Oncogene. 1990 Dec;5(12):1843-50.

Abstract

Precise regulation of proto-oncogene expression appears to be essential for the proper growth and development of multi-cellular organisms. One aspect of this regulation is at the level of transcription from the proto-oncogene promoter(s). In order to characterize the promoter for the chicken c-rel proto-oncogene, we have isolated and sequenced genomic DNA containing the first exon of the chicken c-rel proto-oncogene. The c-rel promoter is structurally similar to the promoters of the so-called house-keeping genes, lacking the CAATT and TATA elements found in some cellular genes, but containing a G/C-rich box near the transcription start sites. There are multiple transcription start sites for the c-rel mRNA, which map near putative binding sites for the transcription factors HIP-1 and NF-kB. The c-rel promoter was functionally characterized by its ability to support expression of the firefly luciferase gene. The c-rel promoter is a relatively weak promoter, 100-times less active than the promoter within the spleen necrosis virus long terminal repeat (LTR). We have defined the c-rel promoter by analysis of a series of 5' deletion mutants of the c-rel promoter fused to the firefly luciferase gene. A DNA fragment containing 97 bp of 5' flanking sequence and 72 bp of 3' flanking sequence is sufficient for c-rel promoter function. Co-transfection of the c-rel promoter with a retroviral vector expressing the c-rel protein resulted in a decrease in expression from the minimal c-rel promoter. These results indicate that expression of the c-rel proto-oncogene is tightly regulated both at the level of basal promoter activity and by autoregulation of transcription by the c-rel protein.

Publication types

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

MeSH terms

  • Adenine / analysis
  • Animals
  • Base Sequence
  • Chickens
  • Chromosome Deletion
  • Cloning, Molecular
  • Cytosine / analysis
  • DNA / analysis
  • DNA / genetics
  • Exons
  • Guanine / analysis
  • Homeostasis / physiology*
  • Luciferases / genetics
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thymine / analysis
  • Transcription, Genetic

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • RNA, Messenger
  • Guanine
  • Cytosine
  • DNA
  • Luciferases
  • Adenine
  • Thymine