DNA binding properties of dioxin receptors in wild-type and mutant mouse hepatoma cells
The current model of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) entails stimulation of target gene transcription via the formation of dioxin-receptor complexes and subsequent accumulation of the complexes within the cell nucleus. Here, the authors have analyzed the DNA binding properties of the dioxin receptor in wild-type mouse hepatoma (Hepa 1c1c7) cells and a class of nonresponsive mutant cells which fail to accumulate dioxin-receptor complexes within the nucleus in vivo. In vitro, both the wild-type and mutant (/sup 3/H)dioxin-receptor complexes exhibited low affinity for DNA-cellulose (5-8% and around 4% retention, respectively) in the absence of prior biochemical manipulations. However, following chromatography on heparin-Sepharose, the wild-type but not the mutant dioxin receptor was transformed to a species with an increased affinity for DNA (40-50% retention on DNA-cellulose). The gross molecular structure of the mutant, non DNA binding dioxin receptor did not appear to be altered as compared to that of the wild-type receptor. These results imply that the primary deficiency in the mutant dioxin receptor form may reside at the DNA binding level and that, in analogy to steroid hormone receptors, DNA binding of the receptor may be an essential step in the regulation of target gene transcription by dioxin.
- Research Organization:
- Huddinge Univ. Hospital (Sweden)
- OSTI ID:
- 7252541
- Journal Information:
- Biochemistry; (United States), Vol. 27:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
DIOXIN
GENETIC EFFECTS
DNA
CONFIGURATION INTERACTION
RECEPTORS
MOLECULAR STRUCTURE
GENE REGULATION
HEPATOMAS
IN VITRO
LIVER CELLS
MICE
TRANSCRIPTION
TRITIUM COMPOUNDS
TUMOR CELLS
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
DISEASES
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques