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Influence of Arsenic on Global Levels of Histone Posttranslational Modifications: a Review of the Literature and Challenges in the Field

Abstract

Arsenic is a human carcinogen and also increases the risk for non-cancer outcomes. Arsenic-induced epigenetic dysregulation may contribute to arsenic toxicity. Although there are several reviews on arsenic and epigenetics, these have largely focused on DNA methylation. Here, we review investigations of the effects of arsenic on global levels of histone posttranslational modifications (PTMs). Multiple studies have observed that arsenic induces higher levels of H3 lysine 9 dimethylation (H3K9me2) and also higher levels of H3 serine 10 phosphorylation (H3S10ph), which regulate chromosome segregation. In contrast, arsenic causes a global loss of H4K16ac, a histone PTM that is a hallmark of human cancers. Although the findings for other histone PTMs have not been entirely consistent across studies, we discuss biological factors which may contribute to these inconsistencies, including differences in the dose, duration, and type of arsenic species examined; the tissue or cell line evaluated; differences by sex; and exposure timing. We also discuss two important considerations for the measurement of histone PTMs: proteolytic cleavage of histones and arsenic-induced alterations in histone expression.

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Acknowledgments

This work was supported by NIH grants P42 ES010349, RO1 CA133595, RO1 ES017875, T32 ES007322, P30 ES009089, and F31ES025100.

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Correspondence to Mary V. Gamble.

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Caitlin G. Howe and Mary V. Gamble declare they have no conflicts of interest.

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Howe, C.G., Gamble, M.V. Influence of Arsenic on Global Levels of Histone Posttranslational Modifications: a Review of the Literature and Challenges in the Field. Curr Envir Health Rpt 3, 225–237 (2016). https://doi.org/10.1007/s40572-016-0104-1

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Keywords

  • Arsenic
  • Histone posttranslational modifications