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Epigenetic Effects of Dietary Trace Elements

  • Epigenetics (ATY Lau, Section Editor)
  • Published:
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Abstract

Purpose of Review

In this review, the recent knowledge regarding the epigenetic effects of the nine most important dietary trace elements will be discussed.

Recent Findings

Although dietary trace elements (iron, zinc, iodine, selenium, copper, manganese, fluoride, chromium, and molybdenum) are incorporated into the human body in tiny amounts, however, they are critical and essential for maintaining normal cellular function and physiology. Aberrant level of these elements, especially when insufficient amount is present in the body, could lead to various human diseases. The biological importance of some of these elements has been noted for many decades, and recent data suggest that they can potentially impact gene expressions by alteration of DNA methylation, histone modifications, and ncRNA expression.

Summary

Essential trace elements are required for the maintenance of epigenetic stability. Therefore, understanding more about the epigenetic effects associated with these dietary trace elements are crucial to finding ways for improving human health.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Holliday R. Epigenetics: a historical overview. Epigenetics. 2006;1(2):76–80.

    Article  PubMed  Google Scholar 

  2. Tran PV, Kennedy BC, Lien YC, et al. Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus. Am J Physiol Regul Integr Comp Physiol. 2015;308(4):R276–82.

    Article  CAS  PubMed  Google Scholar 

  3. Schachtschneider KM, Liu Y, Rund LA, et al. Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development. BMC Genomics. 2016;17(1):856.

    Article  PubMed  PubMed Central  Google Scholar 

  4. • Sangokoya C, Doss JF, Chi JT. Iron-responsive miR-485-3p regulates cellular iron homeostasis by targeting ferroportin. PLoS Genet. 2013;9(4):e1003408. Reports a novel Fe-responsive mechanism for the post-transcriptional regulation of FPN, mediated by miR-485-3p, which is induced during Fe deficiency and represses FPN expression by directly targeting the FPN 3′UTR, to regulate cellular Fe homeostasis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zumbrennen-Bullough KB, Wu Q, Core AB, et al. MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. J Biol Chem. 2014;289(34):23796–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Andreini C, Banci L, Bertini I, et al. Counting the zinc-proteins encoded in the human genome. J Proteome Res. 2006;5(1):196–201.

    Article  CAS  PubMed  Google Scholar 

  7. Fukada T, Yamasaki S, Nishida K, et al. Zinc homeostasis and signaling in health and diseases: zinc signaling. J Biol Inorg Chem. 2011;16(7):1123–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007;117(5):1175–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kuraishy A, Karin M, Grivennikov SI. Tumor promotion via injury- and death-induced inflammation. Immunity. 2011;35(4):467–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tian X, Diaz FJ. Acute dietary zinc deficiency before conception compromises oocyte epigenetic programming and disrupts embryonic development. Dev Biol. 2013;376(1):51–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wong CP, Magnusson KR, Ho E. Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem. 2013;24(1):353–9.

    Article  CAS  PubMed  Google Scholar 

  13. Wong CP, Rinaldi NA, Ho E. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol Nutr Food Res. 2015;59(5):991–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hu YD, Pang W, He CC, et al. The cognitive impairment induced by zinc deficiency in rats aged 0~2 months related to BDNF DNA methylation changes in the hippocampus. Nutr Neurosci. 2016:1–7. doi:10.1080/1028415X.2016.1194554.

  15. Douglas H, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  Google Scholar 

  16. Taccioli C, Chen H, Jiang Y, et al. Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature. Oncogene. 2012;31(42):4550–8.

    Article  CAS  PubMed  Google Scholar 

  17. Alder H, Taccioli C, Chen H, et al. Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer. Carcinogenesis. 2012;33(9):1736–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. • Taccioli C, Garofalo M, Chen H, et al. Repression of esophageal neoplasia and inflammatory signaling by anti-miR-31 delivery in vivo. J Natl Cancer Inst. 2015;107(11):djv220. Zn replenishment or delivery in vivo of anti-miR-31 restored the normal esophageal phenotype, which provides a mechanistic rationale and proof of concept for miR-31 as an epigenetic therapeutic target for ESCC.

    Article  PubMed  PubMed Central  Google Scholar 

  19. • Rodríguez-Rodero S, Delgado-Álvarez E, Díaz-Naya L. Epigenetic modulators of thyroid cancer. Endocrinología Diabetes Y Nutrición. 2017;64(1):44–56. A detailed perspective of the information of epigenetic changes in thyroid cancers on and before the year of 2016.

    Article  Google Scholar 

  20. Wu W, Zhang L, Lin J, et al. Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma. Oncotarget. 2016;7(51):84416–27.

    PubMed  PubMed Central  Google Scholar 

  21. Hong S, Yu S, Li J, et al. MiR-20b displays tumor suppressor functions in papillary thyroid carcinoma by regulating the MAPK/ERK signaling pathway. Thyroid. 2016;26(12):1733–43.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang S, Wang Y, Chen M, et al. CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma. Sci Rep. 2017;7:44033.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Limbach M, Saare M, Tserel L, et al. Epigenetic profiling in CD4+ and CD8+ T cells from Graves’ disease patients reveals changes in genes associated with T cell receptor signaling. J Autoimmun. 2016;67:46–56.

    Article  CAS  PubMed  Google Scholar 

  24. Pohl M, Grabellus F, Worm K, et al. Intermediate microRNA expression profile in Graves’ disease falls between that of normal thyroid tissue and papillary thyroid carcinoma. J Clin Pathol. 2017;70(1):33–9.

    Article  PubMed  Google Scholar 

  25. • Speckmann B, Grune T. Epigenetic effects of selenium and their implications for health. Epigenetics. 2015;10(3):179–90. A detailed perspective of the information of epigenetic effects of Se on and before the year of 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Xing Y, Liu Z, Yang G, et al. MicroRNA expression profiles in rats with selenium deficiency and the possible role of the Wnt/β-catenin signaling pathway in cardiac dysfunction. Int J Mol Med. 2015;35(1):143–52.

    Article  CAS  PubMed  Google Scholar 

  27. Wang X, Hodgkinson CP, Lu K, et al. Selenium augments microRNA directed reprogramming of fibroblasts to cardiomyocytes via Nanog. Sci Rep. 2016;6:23017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Liu M, Hu C, Xu Q, et al. Methylseleninic acid activates Keap1/Nrf2 pathway via up-regulating miR-200a in human oesophageal squamous cell carcinoma cells. Biosci Rep. 2015;35(5):e00256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hu C, Liu M, Zhang W, et al. Upregulation of KLF4 by methylseleninic acid in human esophageal squamous cell carcinoma cells: modification of histone H3 acetylation through HAT/HDAC interplay. Mol Carcinog. 2015;54(10):1051–9.

    Article  CAS  PubMed  Google Scholar 

  30. Wu JC, Wang FZ, Tsai ML, et al. Se-allylselenocysteine induces autophagy by modulating the AMPK/mTOR signaling pathway and epigenetic regulation of PCDH17 in human colorectal adenocarcinoma cells. Mol Nutr Food Res. 2015;59(12):2511–22.

    Article  CAS  PubMed  Google Scholar 

  31. Medici V, Shibata NM, Kharbanda KK, et al. Wilson disease: changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease. Hepatology. 2013;57(2):555–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. • Yu Y, Guerrero CR, Liu S, et al. Comprehensive assessment of oxidatively induced modifications of DNA in a rat model of human Wilson’s disease. Mol Cell Proteomics. 2016;15(3):810–7. Aberrant Cu accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions in Wilson’s disease rat livers and could directly inhibit the activity of Tet enzymes, leading to alteration of epigenetic pathways of gene regulation.

    Article  CAS  PubMed  Google Scholar 

  33. • Ma S, Qing L, Yang X, et al. Expression profiles of long noncoding RNAs and messenger RNAs in Mn-exposed hippocampal neurons of Sprague-Dawley rats ascertained by microarray: implications for Mn-induced neurotoxicity. PLoS One. 2016;11(1):e0145856. Excessive dietary Mn could lead to up-regulation of 135 and down-regulation of 150 lncRNAs in Sprague-Dawley rats hippocampal neurons, in which these lncRNAs are closely related to Mn-induced neurotoxicity.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Yang N, Wei Y, Wang T, et al. Genome-wide analysis of DNA methylation during antagonism of DMOG to MnCl2-induced cytotoxicity in the mouse substantia nigra. Sci Rep. 2016;6:28933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tarale P, Sivanesan S, Daiwile AP, et al. Global DNA methylation profiling of manganese-exposed human neuroblastoma SH-SY5Y cells reveals epigenetic alterations in Parkinson’s disease-associated genes. Arch Toxicol. 2017;91(7):2629–41.

  36. Niu Q, Liu H, Guan Z, et al. The effect of c-Fos demethylation on sodium fluoride-induced apoptosis in L-02 cells. Biol Trace Elem Res. 2012;149(1):102–9.

    Article  CAS  PubMed  Google Scholar 

  37. Daiwile AP, Sivanesan S, Izzotti A, et al. Noncoding RNAs: possible players in the development of fluorosis. Biomed Res Int. 2015;2015:274852.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sun Z, Niu R, Wang B, Wang J. Altered sperm chromatin structure in mice exposed to sodium fluoride through drinking water. Environ Toxicol. 2014;29(6):690–6.

    Article  CAS  PubMed  Google Scholar 

  39. Sun Z, Zhang W, Li S, et al. Altered miRNAs expression profiling in sperm of mice induced by fluoride. Chemosphere. 2016;155:109–14.

    Article  CAS  PubMed  Google Scholar 

  40. • Yin S, Song C, Wu H, et al. Adverse effects of high concentrations of fluoride on characteristics of the ovary and mature oocyte of mouse. PLoS One. 2015;10(6):e0129594. Decreased levels of H3K9ac and H3K18ac and oocyte-specific genes involved in oocyte growth and the induction of the acrosome reaction were observed in female mice with high concentrations of fluoride administration, leading to reduced number of mature oocytes and hampered their development and fertilization.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhu JQ, Si YJ, Cheng LY, et al. Sodium fluoride disrupts DNA methylation of H19 and Peg3 imprinted genes during the early development of mouse embryo. Arch Toxicol. 2014;88(2):241–8.

    Article  CAS  PubMed  Google Scholar 

  42. Zhao L, Zhang S, An X, et al. Sodium fluoride affects DNA methylation of imprinted genes in mouse early embryos. Cytogenet Genome Res. 2015;147(1):41–7.

    Article  PubMed  Google Scholar 

  43. Zhang Q, Sun X, Xiao X, et al. Effects of maternal chromium restriction on the long-term programming in MAPK signaling pathway of lipid metabolism in mice. Nutrients. 2016;8(8):488.

    Article  PubMed Central  Google Scholar 

  44. • Zhang Q, Sun X, Xiao X, et al. Dietary chromium restriction of pregnant mice changes the methylation status of hepatic genes involved with insulin signaling in adult male offspring. PLoS One. 2017;12(1):e0169889. Maternal Cr restriction diet results in glucose intolerance in male offspring through alteration of DNA methylation of hepatic genes associated with the insulin signaling pathway in the mouse livers, suggesting that the adverse effects of Cr deficiency could be propagated epigenetically from one generation to the other.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Schwarz G. Molybdenum cofactor and human disease. Curr Opin Chem Biol. 2016;31:179–87.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Due to space constraints, it has been necessary to cite recent articles wherever possible; our sincere apologies to the hundreds of authors whose primary contributions are therefore not listed. This work was supported by the grants from the National Natural Science Foundation of China (Nos. 31271445 and 31170785), the Science and Technology Planning Project of Guangdong Province of China (No. 2016A020215144), the Guangdong Natural Science Foundation of China (No. S2012030006289), “Thousand, hundred, and ten” project of the Department of Education of Guangdong Province (No. 124), the Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases, and the Colleges and Universities Innovation Project of Guangdong Province of China (Nos. 2016KTSCX041 and 2016KTSCX042). We would like to thank members of the Lau and Xu laboratory for critical reading of this manuscript.

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Authors and Affiliations

  1. Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of China

    Andy T. Y. Lau, Heng Wee Tan & Yan-Ming Xu

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  1. Andy T. Y. Lau
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  2. Heng Wee Tan
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  3. Yan-Ming Xu
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Correspondence to Yan-Ming Xu.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Epigenetics

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Lau, A.T.Y., Tan, H.W. & Xu, YM. Epigenetic Effects of Dietary Trace Elements. Curr Pharmacol Rep 3, 232–241 (2017). https://doi.org/10.1007/s40495-017-0098-x

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  • DOI: https://doi.org/10.1007/s40495-017-0098-x

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