2,3,7,8-Tetrachlorodibenzo-p-dioxin receptors regulate transcription of the cytochrome P1-450 gene
- PMID: 2828385
- DOI: 10.1002/jcb.240350208
2,3,7,8-Tetrachlorodibenzo-p-dioxin receptors regulate transcription of the cytochrome P1-450 gene
Abstract
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) dioxin, produces a diverse set of biological responses which, in some cases, reflects the altered expression of specific genes. An intracellular receptor protein binds TCDD saturably and with high affinity and mediates several of TCDD's biological effects. In mouse hepatoma cells, TCDD induces aryl hydrocarbon hydroxylase activity by activating the transcription of the cytochrome P1-450 gene. Studies of receptor-defective variant cells indicate that the activation of cytochrome P1-450 gene transcription requires functional TCDD receptors. Analysis of the DNA that flanks the 5'-end of the mouse cytochrome P1-450 gene reveals at least three control regions: a promoter, an inhibitory element, and a dioxin-responsive element (DRE). Therefore, expression of the cytochrome P1-450 gene represents a balance between negative and positive control. The DRE contains two discrete, non-overlapping DNA domains that respond to TCDD. Each TCDD-responsive domain acts independently of the other, each requires TCDD receptors for function, and each has the properties of a transcriptional enhancer. For example, the function of the DREs is relatively independent of both their location and their orientation with respect to the promoter. Together, the DREs and the TCDD-receptor complex constitute a dioxin-responsive enhancer system. Exposure of cells to TCDD results in the protection of a specific DNA domain from exonuclease digestion. This protection requires TCDD receptors. The protected domain maps to a DRE. This observation implies that the TCDD-receptor complex interacts with the DRE to activate the transcription of the cytochrome P1-450 gene.
Similar articles
-
Control of cytochrome P1-450 gene expression: analysis of a dioxin-responsive enhancer system.Proc Natl Acad Sci U S A. 1986 May;83(9):2802-6. doi: 10.1073/pnas.83.9.2802. Proc Natl Acad Sci U S A. 1986. PMID: 3010318 Free PMC article.
-
Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer.Proc Natl Acad Sci U S A. 1988 Apr;85(8):2528-32. doi: 10.1073/pnas.85.8.2528. Proc Natl Acad Sci U S A. 1988. PMID: 2833743 Free PMC article.
-
Control of cytochrome P1-450 gene expression by dioxin.Science. 1985 Mar 22;227(4693):1499-502. doi: 10.1126/science.3856321. Science. 1985. PMID: 3856321
-
Induction of hepatic cytochrome P450 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.Mol Biol Med. 1989 Apr;6(2):169-78. Mol Biol Med. 1989. PMID: 2693891 Review.
-
Comparative genetic mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced tumors.Prog Clin Biol Res. 1990;331:177-86. Prog Clin Biol Res. 1990. PMID: 2156270 Review. No abstract available.
Cited by
-
SOCS2-induced proteasome-dependent TRAF6 degradation: a common anti-inflammatory pathway for control of innate immune responses.PLoS One. 2012;7(6):e38384. doi: 10.1371/journal.pone.0038384. Epub 2012 Jun 5. PLoS One. 2012. PMID: 22693634 Free PMC article.
-
Aryl hydrocarbon receptor: The master regulator of immune responses in allergic diseases.Front Immunol. 2022 Dec 19;13:1057555. doi: 10.3389/fimmu.2022.1057555. eCollection 2022. Front Immunol. 2022. PMID: 36601108 Free PMC article. Review.
-
The aryl hydrocarbon receptor complex and the control of gene expression.Crit Rev Eukaryot Gene Expr. 2008;18(3):207-50. doi: 10.1615/critreveukargeneexpr.v18.i3.20. Crit Rev Eukaryot Gene Expr. 2008. PMID: 18540824 Free PMC article. Review.
-
Dietary Indoles Suppress Delayed-Type Hypersensitivity by Inducing a Switch from Proinflammatory Th17 Cells to Anti-Inflammatory Regulatory T Cells through Regulation of MicroRNA.J Immunol. 2016 Feb 1;196(3):1108-22. doi: 10.4049/jimmunol.1501727. Epub 2015 Dec 28. J Immunol. 2016. PMID: 26712945 Free PMC article.
-
2,3,7,8-Tetrachlorodibenzo-p-dioxin induces multigenerational alterations in the expression of microRNA in the thymus through epigenetic modifications.PNAS Nexus. 2022 Dec 9;2(1):pgac290. doi: 10.1093/pnasnexus/pgac290. eCollection 2023 Jan. PNAS Nexus. 2022. PMID: 36712935 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources