Document Type

Article

Peer Reviewed

1

Publication Date

8-11-2014

NLM Title Abbreviation

Int J Mol Sci

Journal/Book/Conference Title

International Journal of Molecular Sciences

PubMed ID

25116688

DOI of Published Version

10.3390/ijms150813916

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.

Keywords

OAfund, aryl hydrocarbon receptor, chromatin accessibility, DNA methylation, epigenetic regulation, polychlorinated biphenyls

Journal Article Version

Version of Record

Published Article/Book Citation

International Journal of Molecular Sciences 15:8 (2014) pp. 13916-13931. doi:10.3390/ijms150813916

Rights

© 2014 by the authors; licensee MDPI, Basel, Switzerland.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Radiology Commons

Share

COinS
 

URL

http://ir.uiowa.edu/radiationoncology_pubs/1