Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 11th Floor, 722 W. 168th Street, New York, NY, 10032, USA.
Curr Environ Health Rep. 2016 Sep;3(3):225-37. doi: 10.1007/s40572-016-0104-1.
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.
砷是一种人类致癌物质，也会增加非癌症结果的风险。砷诱导的表观遗传失调可能导致砷毒性。尽管有几篇关于砷和表观遗传学的综述，但这些综述主要集中在 DNA 甲基化上。在这里，我们回顾了砷对组蛋白翻译后修饰（PTM）整体水平的影响的研究。多项研究观察到，砷诱导 H3 赖氨酸 9 二甲基化（H3K9me2）水平升高，同时 H3 丝氨酸 10 磷酸化（H3S10ph）水平升高，这两种修饰调节染色体分离。相比之下，砷导致 H4K16ac 的整体缺失，H4K16ac 是人类癌症的一个标志。尽管其他组蛋白 PTM 的研究结果在不同研究中并不完全一致，但我们讨论了可能导致这些不一致的生物学因素，包括所研究的砷物种的剂量、持续时间和类型、评估的组织或细胞系、性别差异以及暴露时间的差异。我们还讨论了测量组蛋白 PTM 的两个重要考虑因素：组蛋白的蛋白水解切割和砷诱导的组蛋白表达改变。
