World Health Organization. Arsenic and arsenic compounds. IARC Monographs. 2012;100C.
National Research Council. Critical aspects of EPA's IRIS assessment of inorganic arsenic. National Research Council Interim Report. 2013.
World Health Organization. Arsenic Fact Sheet No 372. 2012.
Kile ML, Houseman EA, Breton CV, Smith T, Quamruzzaman Q, Rahman M. Dietary arsenic exposure in bangladesh. Environ Health Perspect. 2007;115(6):889–93.
Kurzius-Spencer M, Burgess JL, Harris RB, et al. Contribution of diet to aggregate arsenic exposures—An analysis across populations. J Expo Sci Environ Epidemiol. 2014;24(2):156–62.
Challenger F. Biological methylation. Chem Rev. 1945;36(3):315–61.
Hall MN, Gamble MV. Nutritional manipulation of one-carbon metabolism: effects on arsenic methylation and toxicity. J Toxicol. 2012;2012.
Raml R, Rumpler A, Goessler W, et al. Thio-dimethylarsinate is a common metabolite in urine samples from arsenic-exposed women in Bangladesh. Toxicol Appl Pharmacol. 2007;222(3):374–80.
Steinmaus CM, Ferreccio C, Romo JA, et al. Drinking water arsenic in northern Chile: high cancer risks 40 years after exposure cessation. Cancer Epidemiol Biomark Prev. 2013;22(4):623–30. This study demonstrated that cancer risks persist decades after arsenic exposure has been reduced, indicating the need for public health interventions which complement arsenic remediation efforts.
Rossman TG. Mechanism of arsenic carcinogenesis: an integrated approach. Mutat Res. 2003;533(1):37–65.
Ren X, McHale CM, Skibola CF, et al. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect. 2011;119(1):11.
Brookes E, Shi Y. Diverse epigenetic mechanisms of human disease. Annu Rev Genet. 2014;48:237–68.
Falchi L, Verstovsek S, Ravandi-Kashani F, et al. The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy. Cancer. 2015.
Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128(4):635–8.
Chen R, Kang R, Fan XG, et al. Release and activity of histone in diseases. Cell Death Dis. 2014;5:e1370.
Luger K, Mader AW, Richmond RK, et al. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature. 1997;389(6648):251–60.
Cedar H, Bergman Y. Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009;10(5):295–304.
Mersfelder EL, Parthun MR. The tale beyond the tail: histone core domain modifications and the regulation of chromatin structure. Nucleic Acids Res. 2006;34(9):2653–62.
Xu YM, Du JY, Lau AT. Posttranslational modifications of human histone H3: an update. Proteomics. 2014;14(17-18):2047–60. This review summarizes all of the posttranslational histone modifications that have been identified on histone H3.
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95.
Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293(5532):1074–80.
Dai H, Wang Z. Histone modifications patterns and their responses to environment. Curr Environ Health Rep. 2014;1(1):11–21.
Zhang Q, Ramlee MK, Brunmeir R, Villanueva CJ, Halperin D, Xu F. Dynamic and distinct histone modifications modulate the expression of key adipogenesis regulatory genes. Cell Cycle. 2012;11(23):4310–22.
Arita A, Niu J, Qu Q, et al. Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel. Environ Health Perspect. 2012;120(2):198–203.
Reichard JF, Puga A. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation. Epigenomics. 2010;2(1):87–104.
Arita A, Costa M. Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics. 2009;1(3):222–8.
Paul S, Giri AK. Epimutagenesis: A prospective mechanism to remediate arsenic-induced toxicity. Environ Int. 2015;81:8–17.
Argos M. Arsenic Exposure and Epigenetic Alterations: Recent Findings Based on the Illumina 450K DNA Methylation Array. Curr Environ Health Rep. 2015;2(2):137–44.
Arrigo AP. Acetylation and methylation patterns of core histones are modified after heat or arsenite treatment of Drosophila tissue culture cells. Nucleic Acids Res. 1983;11(5):1389–404.
Desrosiers R, Tanguay RM. Further characterization of the posttranslational modifications of core histones in response to heat and arsenite stress in Drosophila. Biochem Cell Biol. 1986;64(8):750–7.
Li J, Chen P, Sinogeeva N, et al. Arsenic trioxide promotes histone H3 phosphoacetylation at the chromatin of CASPASE-10 in acute promyelocytic leukemia cells. J Biol Chem. 2002;277(51):49504–10.
Ramirez T, Brocher J, Stopper H, Hock R. Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells. Chromosoma. 2008;117(2):147–57.
Zhou X, Sun H, Ellen TP, Chen H, Costa M. Arsenite alters global histone H3 methylation. Carcinogenesis. 2008;29(9):1831–6.
Zhou X, Li Q, Arita A, Sun H, Costa M. Effects of nickel, chromate, and arsenite on histone 3 lysine methylation. Toxicol Appl Pharmacol. 2009;236(1):78–84.
Chu F, Ren X, Chasse A, et al. Quantitative mass spectrometry reveals the epigenome as a target of arsenic. Chem Biol Interact. 2011;192(1):113–7.
Herbert KJ, Holloway A, Cook AL, Chin SP, Snow ET. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes. Toxicol Appl Pharmacol. 2014;281(1):136–45.
Rahman S, Housein Z, Dabrowska A, Mayan MD, Boobis AR, Hajji N. E2F1-mediated FOS induction in arsenic trioxide-induced cellular transformation: effects of global H3K9 hypoacetylation and promoter-specific hyperacetylation in vitro. Environ Health Perspect. 2015;123(5):484–92.
Perkins C, Kim CN, Fang G, Bhalla KN. Arsenic induces apoptosis of multidrug-resistant human myeloid leukemia cells that express Bcr-Abl or overexpress MDR, MRP, Bcl-2, or Bcl-xL. Blood. 2000;95(3):1014–22.
Ray PD, Huang BW, Tsuji Y. Coordinated regulation of Nrf2 and histone H3 serine 10 phosphorylation in arsenite-activated transcription of the human heme oxygenase-1 gene. Biochim Biophys Acta. 2015;10(88):18.
Treas JN, Tyagi T, Singh KP. Effects of chronic exposure to arsenic and estrogen on epigenetic regulatory genes expression and epigenetic code in human prostate epithelial cells. PLoS ONE. 2012;7(8):e43880.
Jo WJ, Ren X, Chu F, et al. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure. Toxicol Appl Pharmacol. 2009;241(3):294–302.
Kim HG, Kim DJ, Li S, et al. Polycomb (PcG) proteins, BMI1 and SUZ12, regulate arsenic-induced cell transformation. J Biol Chem. 2012;287(38):31920–8.
Suzuki T, Miyazaki K, Kita K, Ochi T. Trivalent dimethylarsenic compound induces histone H3 phosphorylation and abnormal localization of Aurora B kinase in HepG2 cells. Toxicol Appl Pharmacol. 2009;241(3):275–82.
Suzuki T, Kita K, Ochi T. Phosphorylation of histone H3 at serine 10 has an essential role in arsenite-induced expression of FOS, EGR1 and IL8 mRNA in cultured human cell lines. J Appl Toxicol. 2013;33(8):746–55.
Ge Y, Gong Z, Olson JR, Xu P, Buck MJ, Ren X. Inhibition of monomethylarsonous acid (MMA III)-induced cell malignant transformation through restoring dysregulated histone acetylation. Toxicology. 2013;312:30–5.
Kannan-Thulasiraman P, Katsoulidis E, Tallman MS, Arthur JS, Platanias LC. Activation of the mitogen-and stress-activated kinase 1 by arsenic trioxide. J Biol Chem. 2006;281(32):22446–52.
Cobo JM, Valdez JG, Gurley LR. Inhibition of mitotic-specific histone phosphorylation by sodium arsenite. Toxicol in Vitro. 1995;9(4):459–65.
Liu D, Wu D, Zhao L, et al. Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells. PLoS ONE. 2015;10(10):e0141014.
Cronican AA, Fitz NF, Carter A, et al. Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic. PLoS ONE. 2013;8(2):e53478.
Tyler CR, Hafez AK, Solomon ER, Allan AM. Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region-and sex-specific manner in the adult mouse brain. Toxicol Appl Pharmacol. 2015;288(1):40–51. This is the first animal study to examine the effects of arsenic on PTMs separately by sex and in different tissue types.
Cantone L, Nordio F, Hou L, et al. Inhalable Metal-Rich Air Particles and Histone H 3 K 4 Dimethylation and H 3 K 9 Acetylation in a Cross-sectional Study of Steel Workers. Environ Health Perspect. 2011;119(7):964–9.
Chervona Y, Hall MN, Arita A, et al. Associations between arsenic exposure and global posttranslational histone modifications among adults in Bangladesh. Cancer Epidemiol Biomark Prev. 2012;21(12):2252–60.
Howe, CG, Liu, X, Hall, MN, et al. Associations between blood and urine arsenic concentrations and post-translational histone modifications in Bangladeshi men and women. Environ Health Perspect. 2016. This is the first large human study to evaluate the effects of arsenic exposure, due to arsenic-contaminated drinking water, on PTMs separately by sex
Ma, L, Li, J, Zhan, Z, et al. Specific histone modification responds to arsenic-induced oxidative stress. Toxicol Appl Pharmacol. 2016. This is the first large human study to evaluate the effects of arsenic exposure, due to use of arsenic-contaminated coal, on histone PTMs. This study also evaluated the effect of short versus long duration arsenic exposures on the same PTMs in vitro
Pournara, A, Kippler, M, Holmlund, T, et al. Arsenic alters global histone modifications in lymphocytes in vitro and in vivo. Cell Biol Toxicol. 2016. This is the first human study to evaluate the effects of arsenic exposure on histone PTMs in sorted lymphocytes.
Ernst J, Kheradpour P, Mikkelsen TS, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473(7345):43–9.
Barski A, Cuddapah S, Cui K, et al. High-resolution profiling of histone methylations in the human genome. Cell. 2007;129(4):823–37.
Wang Z, Zang C, Rosenfeld JA. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008;40(7):897–903.
Rivera, C, Saavedra, F, Alvarez, F, et al. Methylation of histone H3 lysine 9 occurs during translation. Nucleic Acids Res. 2015;gkv929.
Yuan W, Xu M, Huang C, Liu N, Chen S, Zhu B. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem. 2011;286(10):7983–9.
Wagner EJ, Carpenter PB. Understanding the language of Lys36 methylation at histone H3. Nat Rev Mol Cell Biol. 2012;13(2):115–26.
Jha DK, Pfister SX, Humphrey TC, Strahl BD. SET-ting the stage for DNA repair. Nat Struct Mol Biol. 2014;21(8):655–7.
Kuo AJ, Cheung P, Chen K, et al. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol Cell. 2011;44(4):609–20.
Pfister SX, Markkanen E, Jiang Y, et al. Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation. Cancer Cell. 2015;28(5):557–68.
Nguyen AT, Zhang Y. The diverse functions of Dot1 and H3K79 methylation. Genes Dev. 2011;25(13):1345–58.
Daigle SR, Olhava EJ, Therkelsen CA, et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood. 2013;122(6):1017–25.
Bernt KM, Zhu N, Sinha AU, et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation b DOT1L. Cancer Cell. 2012;20(1):66–78.
Shahbazian MD, Grunstein M. Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem. 2007;76:75–100.
Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science. 2006;311(5762):844–7.
Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 2005;37(4):391–400.
Prigent C, Dimitrov S. Phosphorylation of serine 10 in histone H3, what for? J Cell Sci. 2003;116(18):3677–85.
Jiang X, Chen C, Zhao W, Zhang Z. Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: an implication for the paradoxical mechanism. Environ Toxicol Pharmacol. 2013;36(3):891–902.
Styblo M, Del Razo LM, Vega L. Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol. 2000;74(6):289–99.
Vahter M. Species differences in the metabolism of arsenic compounds. Appl Organomet Chem. 1994;8(3):175–82.
Faulk C, Dolinoy DC. Timing is everything: the when and how of environmentally induced changes in the epigenome of animals. Epigenetics. 2011;6(7):791–7.
Ahsan H, Chen Y, Parvez F, et al. Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal Study. Am J Epidemiol. 2006;163:1138–48.
Chen Y-C, Guo Y-LL SH-JJ, et al. Arsenic methylation and skin cancer risk in southwestern Taiwan. J Occup Environ Med. 2003;45:241–8.
Gardner RM, Kippler M, Tofail F, et al. Environmental exposure to metals and children’s growth to age 5 years: a prospective cohort study. Am J Epidemiol. 2013;177(12):1356–67.
Hamadani JD, Tofail F, Nermell B, et al. Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study. Int J Epidemiol. 2011;40(6):1593–604.
Moon KA, Guallar E, Umans JG, et al. Association between exposure to low to moderate arsenic levels and incident cardiovascular disease. A prospective cohort study. Ann Intern Med. 2013;159(10):649–59.
Broberg K, Ahmed S, Engstrom K, et al. Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys. J Dev Orig Health Dis. 2014;5(04):288–98. This study examined the effects of arsenic on genome-wide DNA methylation in cord blood separately by sex and observed that the effects were more pronounced among boys.
Pilsner JR, Hall MN, Liu X, et al. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA. PLoS One. 2012;7(5):e37147. This study examined the effects of arsenic on global DNA methylation levelsof DNA methylation in cord blood separately by sex and observed that the effects were in opposite directions for boys and girls.
Niedzwiecki MM , Liu X, Hall MN. Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh. Cancer Epidemiol Biomark Prev. 2015; 24(11):1748-1757. This was the first human study to examine the effects of arsenic on both 5-methylcytosine and 5-hydroxymethylcytosine. Differences by sex were evaluated and the associations between arsenic and these marks differed between men and women.
Nohara K, Baba T, Murai H, et al. Global DNA methylation in the mouse liver is affected by methyl deficiency and arsenic in a sex-dependent manner. Arch Toxicol. 2011;85(6):653–61.
Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28(7):778–808.
Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005;437(7057):436–9.
Miller VM, Kaplan JR, Schork NJ. Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists. Biol Sex Differ. 2011;2:14.
Bellott DW, Hughes JF, Skaletsky H, et al. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature. 2014;508(7497):494.
Dhaenens M, Glibert P, Meert P, Vossaert L, Deforce D. Histone proteolysis: a proposal for categorization into ‘clipping’and ‘degradation’. Bioessays. 2015;37(1):70–9. This is a very comphrensive review of all of studies which have identified histone proteolysis and it provides important discussion about the difficulties in distinguishing between biological histone clipping versus histone degradation.
Azad GK, Tomar RS. Proteolytic clipping of histone tails: the emerging role of histone proteases in regulation of various biological processes. Mol Biol Rep. 2014;41(5):2717–30.
Zhou P, Wu E, Alam HB, Li Y. Histone cleavage as a mechanism for epigenetic regulation: current insights and perspectives. Curr Mol Med. 2014;14(9):1164–72.
Howe CG, Gamble MV. Enzymatic cleavage of histone H3: a new consideration when measuring histone modifications in human samples. Clin Epigenetics. 2015;7(1):1. This letter presents evidence that histone H3 is cleaved in human peripheral blood mononuclear cells and demonstrates that this influences the measurement of certain PTMs.
Brocato J, Fang L, Chervona Y, et al. Arsenic induces polyadenylation of canonical histone mRNA by down-regulating stem-loop-binding protein gene expression. J Biol Chem. 2014;289(46):31751–64. This study demonstrated that arsenic increases the expression of the canonical histone proteins.
Hake SB, Garcia BA, Duncan EM, et al. Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem. 2006;281(1):559–68.
Thambirajah AA, Li A, Ishibashi T, Ausio J. New developments in post-translational modifications and functions of histone H2A variants. Biochem Cell Biol. 2009;87(1):7–17.
Yih LH, Hsueh SW, Luu WS, Chiu TS, Lee TC. Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells. Carcinogenesis. 2005;26(1):53–63.
Xie H, Huang S, Martin S, Wise Sr JP. Arsenic is cytotoxic and genotoxic to primary human lung cells. Mutat Res Genet Toxicol Environ Mutagen. 2014;760:33–41.
Rehman K, Fu YJ, Zhang YF, et al. Trivalent methylated arsenic metabolites induce apoptosis in human myeloid leukemic HL-60 cells through generation of reactive oxygen species. Metallomics. 2014;6(8):1502–12.
Brocato J, Chen D, Liu J, Fang L, Jin C, Costa M. A Potential New Mechanism of Arsenic Carcinogenesis: Depletion of Stem-Loop Binding Protein and Increase in Polyadenylated Canonical Histone H3.1 mRNA. Biol Trace Elem Res. 2015;166(1):72–81.
Rea, M, Jiang, T, Eleazer, R, et al. Quantitative mass spectrometry reveals changes in histone H2B variants as cells undergo inorganic arsenic-mediated cellular transformation. Mol Cell Proteomics. 2016. This is the first study to demonstrate that arsenic differentially alters H2B variants.
Sadhu MJ, Guan Q, Li F, et al. Nutritional control of epigenetic processes in yeast and human cells. Genetics. 2013;195(3):831–44.
Garcia BA, Luka Z, Loukachevitch LV, Bhanu NV, Wagner C. Folate deficiency affects histone methylation. Med Hypotheses. 2016;88:63–7.
Lambrot R, Xu C, Saint-Phar S, et al. Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes. Nat Commun. 2013;4:2889.
Mehedint MG, Niculescu MD, Craciunescu CN, Zeisel SH. Choline deficiency alters global histone methylation and epigenetic marking at the Re1 site of the calbindin 1 gene. FASEB J. 2010;24(1):184–95.
Davison JM, Mellott TJ, Kovacheva VP, Blusztajn JK. Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain. J Biol Chem. 2009;284(4):1982–9.
Pilsner JR, Liu X, Ahsan H, et al. Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults. Am J Clin Nutr. 2007;86(4):1179–86.
Lambrou A, Baccarrelli A, Wright RO, et al. Arsenic exposure and DNA methylation among elderly men. Epidemiology. 2012;23(5):668.