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Characterization of Epigenetic Changes as cells undergo inorganic arsenic-mediated
transformation
Matthew Rea1 and Yvonne Fondufe-Mittendorf1
1
Department of Molecular and Cellular Biochemistry, University of Kentucky
Background and Objective: Inorganic arsenic (iAs) is a ubiquitous environmental toxicant
implicated in carcinogenesis. Epigenetic regulation is a potential mechanism by which iAs
causes cancer To decipher this mechanism, we carried out high resolution profiling of the
epigenetic changes as cells go through iAs-mediated cellular transformation.
Methods: Two high-resolution methods were used to profile these epigenetic changes: topdown mass spectrometry to quantify the changes in the levels of H2B variants and Methyl-seq
to identify DNA methylation.
Results: iAs exposure induces carcinogenic transformation as seen in changes to EMT
markers. We also identified changes in the expression levels of specific Histone H2B variants in
these cell types, which were both time and dose-dependent. Although no global change in DNA
methylation levels was observed, differential methylation was seen at specific loci in iAstransformed cells suggesting that iAs targets specific gene loci.
Discussion and Conclusions: Our observation of changes in expression of some H2B
variants and DNA methylation levels in iAs-transformed cells might drive the carcinogenic
potential of iAs. Further studies will be carried out to determine the target genes of epigenetic
changes during iAs-transformation. These analyses provide the first step towards understanding
the functional significance of epigenetic changes in iAs-mediated transformation. Additionally,
they set a platform for the development of potential therapeutics in iAs-carcinogenesis.
This work was supported by grants NSF (MCB 1517986) and NIEHS (R01-ES024478).