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Int. J. Mol. Sci. 2014, 15(8), 13916-13931; doi:10.3390/ijms150813916

Epigenetic Determinants of CYP1A1 Induction by the Aryl Hydrocarbon Receptor Agonist 3,3',4,4',5-Pentachlorobiphenyl (PCB 126)

1
Interdisciplinary Graduate Program in Human Toxicology, the University of Iowa, Iowa City, IA 52242, USA
2
Department of Radiation Oncology, the University of Iowa, Iowa City, IA 52242, USA
3
Summer Undergraduate Research Program, Interdisciplinary Graduate Program in Molecular and Cellular Biology, the University of Iowa, Iowa City, IA 52242, USA
*
Author to whom correspondence should be addressed.
Received: 4 June 2014 / Revised: 6 August 2014 / Accepted: 7 August 2014 / Published: 11 August 2014
(This article belongs to the Special Issue Mechanisms of Toxicity of Dioxins and Related Compounds)
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Abstract

Many enzymes involved in xenobiotic metabolism, including cytochrome P450 (CYP) 1A1, are regulated by the aryl hydrocarbon receptor (AhR). 3,3',4,4',5-Penta chlorobiphenyl (PCB 126) is a potent ligand for AhR and can thus induce the expression of CYP1A1. Interestingly, we observed that human carcinoma cell lines derived from different types of epithelial cells displayed divergent degrees of CYP1A1 induction after exposure to PCB 126. Since epigenetic mechanisms are known to be involved in cell type-specific gene expression, we sought to assess the epigenetic determinants of CYP1A1 induction in these carcinoma cell lines. In contrast to HepG2 hepatocarcinoma cells, HeLa cervical carcinoma cells showed significantly lower levels of CYP1A1 mRNA expression following PCB 126 exposure. Our results show that the two cell lines maintained differences in the chromatin architecture along the CYP1A1 promoter region. Furthermore, treatment with the epigenetic modifiers, trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-Aza-dC), significantly increased the expression of CYP1A1 after PCB 126 treatment in HeLa cells. However, we did not observe apparent differences in methylation levels or specific location of CpG DNA methylation between the two cell lines in the analyzed CYP1A1 promoter region. Taken together, our findings suggest that the differences in CYP1A1 expression between HepG2 and HeLa cells are due to differences in the chromatin architecture of the CYP1A1 promoter and thus establish a role of epigenetic regulation in cell-specific CYP1A1 expression. View Full-Text
Keywords: aryl hydrocarbon receptor; chromatin accessibility; DNA methylation; epigenetic regulation; polychlorinated biphenyls aryl hydrocarbon receptor; chromatin accessibility; DNA methylation; epigenetic regulation; polychlorinated biphenyls
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Vorrink, S.U.; Hudachek, D.R.; Domann, F.E. Epigenetic Determinants of CYP1A1 Induction by the Aryl Hydrocarbon Receptor Agonist 3,3',4,4',5-Pentachlorobiphenyl (PCB 126). Int. J. Mol. Sci. 2014, 15, 13916-13931.

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