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9-15-2017 Transient and Permanent Changes in DNA Methylation Patterns in Inorganic Arsenic- Mediated Epithelial-to-Mesenchymal Transition Meredith Eckstein University of Kentucky, [email protected]

Matthew Rea University of Kentucky, [email protected]

Yvonne N. Fondufe-Mittendorf University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits oy u.

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Repository Citation Eckstein, Meredith; Rea, Matthew; and Fondufe-Mittendorf, Yvonne N., "Transient and Permanent Changes in DNA Methylation Patterns in Inorganic Arsenic-Mediated Epithelial-to-Mesenchymal Transition" (2017). Molecular and Cellular Biochemistry Faculty Publications. 157. https://uknowledge.uky.edu/biochem_facpub/157

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Notes/Citation Information Published in Toxicology and Applied Pharmacology, v. 331, p. 6-17.

© 2017 The Authors. Published by Elsevier Inc

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/).

Digital Object Identifier (DOI) https://doi.org/10.1016/j.taap.2017.03.017

This article is available at UKnowledge: https://uknowledge.uky.edu/biochem_facpub/157 Toxicology and Applied Pharmacology 331 (2017) 6–17

Contents lists available at ScienceDirect

Toxicology and Applied Pharmacology

journal homepage: www.elsevier.com/locate/taap

Transient and permanent changes in DNA methylation patterns in inorganic arsenic-mediated epithelial-to-mesenchymal transition

Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf ⁎

Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA article info abstract

Article history: Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, Received 23 February 2017 which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations Accepted 16 March 2017 have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic Available online 21 March 2017 changes to cells correlate with changes in chromatin structure and expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesen- Keywords: chymal transition and the impact of epigenetic alterations in this process are limited. In this study we used Inorganic arsenic DNA methylation high-resolution microarray analysis to measure the changes in DNA methylation in cells undergoing inorganic Infinium MethylationEPIC BeadChip arsenic-induced epithelial-to-mesenchymal transition, and on the reversal of this process, after removal of the EMT inorganic arsenic exposure. We found that cells exposed to chronic, low-dose inorganic arsenic exposure showed Epigenetics 30,530 sites were differentially methylated, and with inorganic arsenic withdrawal several differential methylat- ed sites were reversed, albeit not completely. Furthermore, these changes in DNA methylation mainly correlated with changes in gene expression at most sites tes