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Ligand-dependent interaction of the dioxin receptor with target DNA
S Cuthill1, J Hapgood, M Denis
1Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Abstract:
Wild type and nuclear transfer deficient mouse hepatoma cell lines were used to study the specific DNA binding of a dioxin inducible factor. This factor interacts with XRE only after dioxin treatment and is absent in receptor mutant containing cells even after treatment. Thus, evidence is provided to substantiate the claim that the dioxin receptor is involved in the specific DNA interaction with dioxin response enhancer elements. It is also shown that the molybdate stabilised dioxin-receptor interacts with hsp90 suggesting that, in similarity to the glucocorticoid receptor, the dioxin receptor is kept in a non-transformed state in the absence of ligand.
Insights
The dioxin receptor binds DNA specifically to dioxin response elements after dioxin exposure. This receptor, similar to the glucocorticoid receptor, is maintained in an inactive state by hsp90 until ligand binding.
Area of Science:
- Molecular Biology
- Toxicology
- Cell Biology
Background:
- Dioxin exposure triggers cellular responses mediated by a specific receptor.
- The precise mechanism of dioxin receptor interaction with DNA and its regulation remains under investigation.
Purpose of the Study:
- To investigate the specific DNA binding of the dioxin-inducible factor.
- To elucidate the role of the dioxin receptor in DNA interaction with dioxin response enhancer elements.
- To explore the interaction of the dioxin-receptor with hsp90 and its implications for ligand-independent regulation.
Main Methods:
- Utilized wild type and nuclear transfer deficient mouse hepatoma cell lines.
- Analyzed dioxin-inducible factor interaction with DNA sequences (XRE).
- Examined receptor behavior in the presence and absence of dioxin and in mutant cell lines.
- Investigated the interaction between molybdate-stabilized dioxin-receptor and hsp90.
Main Results:
- The dioxin-inducible factor specifically binds to XRE only after dioxin treatment.
- This DNA binding activity was absent in receptor mutant cells, even after dioxin exposure.
- Evidence confirms the dioxin receptor's crucial role in specific DNA interaction with dioxin response enhancer elements.
- The molybdate-stabilized dioxin-receptor was shown to interact with hsp90.
Conclusions:
- The dioxin receptor is essential for the specific DNA binding to dioxin response enhancer elements.
- The dioxin receptor, analogous to the glucocorticoid receptor, is maintained in a non-transformed state by hsp90 in the absence of its ligand.