Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and inducer-dependent transcription enhancer. Academic Article uri icon

Overview

MeSH

  • Acetylcysteine
  • Alkaloids
  • Animals
  • Base Sequence
  • Binding Sites
  • Consensus Sequence
  • DNA-Binding Proteins
  • Enzyme Induction
  • Genes
  • Genistein
  • Isoflavones
  • L Cells (Cell Line)
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Proteins
  • Phenols
  • Polycyclic Compounds
  • Protein Kinase Inhibitors
  • Rats
  • Recombinant Fusion Proteins
  • Repetitive Sequences, Nucleic Acid
  • Staurosporine
  • Transcription Factor AP-1
  • Transcription Factors
  • Tumor Cells, Cultured

MeSH Major

  • Enhancer Elements, Genetic
  • Heme Oxygenase (Decyclizing)
  • Naphthalenes
  • Transcription, Genetic

abstract

  • A 161-base pair fragment (AB1) approximately 10 kilobase pairs upstream of the transcription start site of the mouse heme oxygenase-1 gene functions as a basal level and inducer-dependent enhancer. AB1/chloramphenicol acetyltransferase fusion genes stably transfected into mouse hepatoma (Hepa) cells or L929 fibroblasts were activated 7-8- or 17-22-fold, respectively, after treatment of the cells with either CdCl2 or heme. The AB1 fragment is composed largely of three tandem repeats containing two conserved core elements, A and B. Part of core element A (TCCGGAGCTGTG) resembles the consensus-binding site for transcription factor AP-4, whereas core element B (GCTGAGTCANGG) includes the consensus-binding site (TGAGTCA) for the AP-1 family of transcription factors. Nuclear proteins from Hepa cells did not bind to any of the core A elements, but bound to all three copies of the core B element. AB1 derivatives with one or two mutant AP-1-binding elements exhibited reduced but measurable inducer-dependent enhancer activity, but mutation of all three AP-1-binding sites abolished activation by CdCl2 and heme and also by mercury chloride, zinc chloride, H2O2, sodium arsenate, and 12-O-tetradecanoylphorbol-13-acetate. Pretreatment of stably transfected L929 cells with protein kinase C inhibitors, but not with tyrosine kinase inhibitors or N-acetylcysteine, abrogated 12-O-tetradecanoylphorbol-13-acetate-dependent activation of the AB1/chloramphenicol acetyltransferase fusion gene. Induction by H2O2 was unaffected by the kinase inhibitors, but completely abolished by N-acetylcysteine. Heme-dependent induction was not significantly affected by any of these chemicals.

publication date

  • May 19, 1995

has subject area

  • Acetylcysteine
  • Alkaloids
  • Animals
  • Base Sequence
  • Binding Sites
  • Consensus Sequence
  • DNA-Binding Proteins
  • Enhancer Elements, Genetic
  • Enzyme Induction
  • Genes
  • Genistein
  • Heme Oxygenase (Decyclizing)
  • Isoflavones
  • L Cells (Cell Line)
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Naphthalenes
  • Nuclear Proteins
  • Phenols
  • Polycyclic Compounds
  • Protein Kinase Inhibitors
  • Rats
  • Recombinant Fusion Proteins
  • Repetitive Sequences, Nucleic Acid
  • Staurosporine
  • Transcription Factor AP-1
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 7538129

Additional Document Info

start page

  • 11977

end page

  • 11984

volume

  • 270

number

  • 20