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Down-regulation of the major histocompatibility complex class-I enhancer in adenovirus type 12-transformed cells is accompanied by an increase in factor binding

Academic Article
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Overview

authors

  • Ge, R. W.
  • Kralli, Anastasia
  • Weinmann, R.
  • Ricciardi, R. P.

publication date

  • December 1992

journal

  • Journal of Virology  Journal

abstract

  • In transformed cells, the E1A gene of adenovirus type 12 (Ad12) represses transcription of class I genes of the major histocompatibility complex. The tumorigenic potential of Ad12-transformed cells correlates with this diminished class I expression. In contrast, the E1A gene of the nontumorigenic Ad5 does not affect class I expression. We show here that a transfected reporter chloramphenicol acetyltransferase plasmid driven by an H-2K promoter (-1049 bp) was expressed at much lower levels in Ad12- than in Ad5-transformed mouse cells. Analysis of mutant constructs revealed that only 83 bp of H-2 DNA, consisting of the enhancer juxtaposed to the basal promoter, was sufficient for this differential expression. Whereas the H-2 basal promoter alone was somewhat less active in Ad12-transformed cells, the H-2 TATA box itself did not appear to be important. The H-2 enhancer proved to be the principal element in Ad12 E1A-mediated repression, since (i) substitution of the H-2 enhancer by simian virus 40 enhancers overcame the repression, and (ii) when juxtaposed to either its native or heterologous basal promoters, the H-2 enhancer was functional in Ad5- but not Ad12-transformed cells. Mobility shift assays showed that there is a DNA-binding activity to the 5' site (R2 element) of the enhancer that is significantly higher in Ad12- than in Ad5-transformed cells. These results suggest that decreased class I enhancer activity in Ad12-transformed cells may, at least in part, be due to the higher levels of an enhancer-specific factor, possibly acting as a repressor.

subject areas

  • Adenovirus E1A Proteins
  • Adenoviruses, Human
  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • Chloramphenicol O-Acetyltransferase
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Viral
  • Genes, MHC Class I
  • Genes, Viral
  • H-2 Antigens
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • Recombinant Proteins
  • TATA Box
  • Transcription, Genetic
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Identity

PubMed Central ID

  • PMC240338

International Standard Serial Number (ISSN)

  • 0022-538X

PubMed ID

  • 1433502
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Additional Document Info

start page

  • 6969

end page

  • 6978

volume

  • 66

issue

  • 12

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