The Effects of Low Selenium on DNA Methylation in the Tissues of Chickens

  • Qiaojian Zhang
  • Shufang Zheng
  • Shengchen Wang
  • Zhihui JiangEmail author
  • Shiwen XuEmail author


DNA methylation is involved in epigenetic mechanisms associated with gene suppression, and its abnormalities lead to gene instability and disease development. As an essential trace element in humans and animals, selenium (Se) is also associated with abnormal changes in DNA methylation. However, the effect of low Se on DNA methylation in avian tissues has not been reported. In the current study, chickens were fed a low-Se diet (0.033 mg Se/kg) or supplemented with 0.15 mg Se/kg as selenite for up to 55 days. DNA methylation levels were examined by high-performance liquid chromatography (HPLC). DNA methyltransferases (DNMTs) and methyl-DpG-binding domain protein 2 (MBD2) mRNA levels were examined through the applications of RT-PCR. The experiment aims to explore the relationship between low Se and DNA methylation. The results showed that total DNA methylation levels in the muscle tissues, brain, immune tissues, and liver of the low-selenium diet group were decreased compared with the control group. The degree of DNA methylation reduction in different tissues from largest to smallest was liver > cerebellum > thymus > brain > spleen ≥ leg muscles > pectoral muscles > bursa of Fabricius > thalamus > wing muscles. DNMT1, DNMT3A, and DNMT3B mRNA expression levels of the low-selenium diet group were decreased compared with those in the control group. The mRNA expression of the MBD2 gene was increased. The results indicate that low Se can reduce the DNA methylation levels of tissues, especially within the liver. These conclusions provide a basis for exploring the pathogenesis of selenium deficiency from the perspective of DNA methylation and create a new basis for comparative medicine.


Chicken Selenium (Se) deficiency DNA methylation DNA methyltransferases (DNMTs) Methyl-DpG-binding domain protein 2 (MBD2) 


Funding Information

This study was supported by the International (Regional) Cooperation and Exchange Projects of the National Natural Science Foundation of China (31320103920) and the National Natural Science Foundation of China (31772814).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Schwarz K, Bieri J, Briggs G, Scott M (1957) Prevention of exudative diathesis in chicks by factor 3 and selenium. Proc Soc Exp Biol Med 95(4):621–625PubMedGoogle Scholar
  2. 2.
    Rayman MP (2000) The importance of selenium to human health. Lancet 356(9225):233–241PubMedGoogle Scholar
  3. 3.
    Kaur R, Ghanghas P, Rastogi P, Kaushal N (2018) Protective role of selenium against hemolytic anemia is mediated through redox modulation. Biol Trace Elem Res 1–11.
  4. 4.
    Malerba M, Cerana R (2018) Effect of selenium on the responses induced by heat stress in plant cell cultures. Plants 7(3):64PubMedCentralGoogle Scholar
  5. 5.
    Zheng L, Jiang W, Feng L, Wu P, Tang L, Kuang S, Zeng Y, Zhou X, Liu Y (2018) Selenium deficiency impaired structural integrity of the head kidney, spleen and skin in young grass carp (Ctenopharyngodon idella). Fish Shellfish Immunol 82:408–420PubMedGoogle Scholar
  6. 6.
    Papadomichelakis G, Zoidis E, Pappas A, Danezis G, Georgiou C, Fegeros K (2018) Dietary organic selenium addition and accumulation of toxic and essential trace elements in liver and meat of growing rabbits. Meat Sci 145:383–388PubMedGoogle Scholar
  7. 7.
    Whanger PD, Weswig PH, Oldfield JE, Cheeke PR, Schmitz JA (1976) Selenium and white muscle disease in lambs: effects of vitamin E and ethoxyquin. Nutr Rep Int 13:159–173Google Scholar
  8. 8.
    Fan R, Cao C, Chen M, Shi Q, Xu S (2018) Gga-let-7f-3p promotes apoptosis in selenium deficiency-induced skeletal muscle by targeting selenoprotein K. Metallomics 10(7):941–952PubMedGoogle Scholar
  9. 9.
    Shan H, Yan R, Diao J, Lin L, Wang S, Zhang M, Zhang R, Wei J (2015) Involvement of caspases and their upstream regulators in myocardial apoptosis in a rat model of selenium deficiency-induced dilated cardiomyopathy. J Trace Elem Med Biol 31:85–91PubMedGoogle Scholar
  10. 10.
    Jabłońska E, Reszka E (2017) Selenium and epigenetics in cancer: focus on DNA methylation. Adv Cancer Res 136:193–234PubMedGoogle Scholar
  11. 11.
    Uthus EO, Ross SA, Davis CD (2006) Differential effects of dietary selenium (Se) and folate on methyl metabolism in liver and colon of rats. Biol Trace Elem Res 109(3):201–214PubMedGoogle Scholar
  12. 12.
    Speckmann B, Schulz S, Hiller F, Hesse D, Schumacher F, Kleuser B, Geisel J, Obeid R, Grune T, Kipp A (2017) Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice. J Nutr Biochem 48:112–119PubMedGoogle Scholar
  13. 13.
    Huawei Z, Lin Y, Wen-Hsing C, Uthus EO (2011) Dietary selenomethionine increases exon-specific DNA methylation of the p53 gene in rat liver and colon mucosa. J Nutr 141(8):1464–1468Google Scholar
  14. 14.
    Arai Y, Ohgane J, Yagi S, Ito R, Iwasaki Y, Saito K, Akutsu K, Takatori S, Ishii R, Hayashi R (2011) Epigenetic assessment of environmental chemicals detected in maternal peripheral and cord blood samples. J Reprod Dev 57(4):507–517PubMedGoogle Scholar
  15. 15.
    Xiang N, Zhao R, Song G, Zhong W (2008) Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells. Carcinogenesis 29(11):2175–2181PubMedPubMedCentralGoogle Scholar
  16. 16.
    Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, Taga T (2001) DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell 1(6):749–758PubMedGoogle Scholar
  17. 17.
    Laird A, Thomson JP, Harrison DJ, Meehan RR (2013) 5-hydroxymethylcytosine profiling as an indicator of cellular state. Epigenomics 5(6):655–669PubMedGoogle Scholar
  18. 18.
    Kulis M, Esteller M (2010) DNA methylation and cancer. Adv Genet 70(22):27PubMedGoogle Scholar
  19. 19.
    Castro R, Rivera I, Struys EA, Jansen EEW, Ravasco P, Camilo ME, Blom HJ, Jakobs C, Almeida ITD (2003) Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem 49(8):1292–1296PubMedGoogle Scholar
  20. 20.
    Cox R, Goorha S (1986) A study of the mechanism of selenite-induced hypomethylated DNA and differentiation of Friend erythroleukemic cells. Carcinogenesis 7(12):2015–2018PubMedGoogle Scholar
  21. 21.
    Metes-Kosik N, Luptak I, Dibello P, Handy D, Tang S, Zhi H, Qin F, Jacobsen D, Loscalzo J, Joseph J (2012) Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res 56(12):1812–1824PubMedPubMedCentralGoogle Scholar
  22. 22.
    Jin X, Jia T, Liu R, Xu S (2018) The antagonistic effect of selenium on cadmium-induced apoptosis via PPAR-γ/PI3K/Akt pathway in chicken pancreas. J Hazard Mater 357:355–362PubMedGoogle Scholar
  23. 23.
    Zhang J, Fu Y, Li J, Wang J, He B, Xu S (2009) Effects of subchronic cadmium poisoning on DNA methylation in hens. Environ Toxicol Pharmacol 27(3):345–349PubMedGoogle Scholar
  24. 24.
    Liu T, Yang T, Xu Z, Tan S, Pan T, Wan N, Li S (2018) MicroRNA-193b-3p regulates hepatocyte apoptosis in selenium-deficient broilers by targeting MAML1. J Inorg Biochem 186:235–245PubMedGoogle Scholar
  25. 25.
    Jie Y, Yuan Z, Hamid S, Cai J, Qi L, Hao L, Zhao R, Hong W, Xu S, Zhang Z (2017) Interplay between autophagy and apoptosis in selenium deficient cardiomyocytes in chicken. J Inorg Biochem 170:17–25Google Scholar
  26. 26.
    Cui J, Zhong R, Chu E, Zhang X, Zhang W, Fang C, Dong Q, Li FL, Li H (2012) Correlation between oxidative stress and L-type calcium channel expression in the ventricular myocardia of selenium-deficient mice. J Int Med Res 40(5):1677–1687PubMedGoogle Scholar
  27. 27.
    Wang J, Lian S, He X, Yu D, Liang J, Sun D, Wu R (2018) Selenium deficiency induces splenic growth retardation by deactivating the IGF-1R/PI3K/Akt/mTOR pathway. Metallomics 10(11):1570–1575PubMedGoogle Scholar
  28. 28.
    Zahrazadeh M, Riasi A, Farhangfar H, Mahyari SA (2018) Effects of close-up body condition score and selenium-vitamin E injection on lactation performance, blood metabolites, and oxidative status in high-producing dairy cows. J Dairy Sci 101(11):10495–10504PubMedGoogle Scholar
  29. 29.
    Dalia AM, Loh TC, Sazili AQ, Jahromi MF, Samsudin AA (2018) Effects of vitamin E, inorganic selenium, bacterial organic selenium, and their combinations on immunity response in broiler chickens. BMC Vet Res 14(1):249PubMedPubMedCentralGoogle Scholar
  30. 30.
    Kumbhar S, Khan AZ, Parveen F, Nizamani ZA, Siyal FA, El-Hack MEA, Gan F, Liu Y, Hamid M, Nido SA (2018) Impacts of selenium and vitamin E supplementation on mRNA of heat shock proteins, selenoproteins and antioxidants in broilers exposed to high temperature. AMB Express 8(1):112PubMedPubMedCentralGoogle Scholar
  31. 31.
    Li W, Tang R, Ma F, Ouyang S, Liu Z, Wu J (2018) Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice. J Nutr Biochem 59:76–83PubMedGoogle Scholar
  32. 32.
    Reik W, Dean W (2001) DNA methylation and mammalian epigenetics. Electrophoresis 22(14):2838–2843PubMedGoogle Scholar
  33. 33.
    Jia Y, Guo M (2013) Epigenetic changes in colorectal cancer. Chin J Cancer 32(1):21–30PubMedPubMedCentralGoogle Scholar
  34. 34.
    Tian F, Luo J, Zhang H, Chang S, Song J (2012) Marek’s disease virus challenge induced immune-related gene expression and chicken repeat 1 (CR1) methylation alterations in chickens. Am J Mol Biol 2(3):232–241Google Scholar
  35. 35.
    Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M (2014) Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33(11):1665–1673Google Scholar
  36. 36.
    Balaghi M, Wagner C (1992) Methyl group metabolism in the pancreas of folate-deficient rats. J Nutr 122(7):1391–1396PubMedGoogle Scholar
  37. 37.
    Bermingham EN, Bassett SA, Young W, Roy NC, Mcnabb WC, Cooney JM, Di TB, Laing WA, Barnett MP (2013) Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets. BMC Med Genet 6(1):1–18Google Scholar
  38. 38.
    de Miranda J, Andrade FO, Conti A, Dagli M, Moreno F, Ong T (2014) Effects of selenium compounds on proliferation and epigenetic marks of breast cancer cells. J Trace Elem Med Biol 28(4):486–491PubMedGoogle Scholar
  39. 39.
    Davis C, Uthus E, Finley J (2000) Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon. J Nutr 130(12):2903–2909PubMedGoogle Scholar
  40. 40.
    Armstrong KM, Bermingham EN, Bassett SA, Treloar BP, Roy NC, Barnett MP (2011) Global DNA methylation measurement by HPLC using low amounts of DNA. Biotechnol J 6(1):113–117PubMedGoogle Scholar
  41. 41.
    Jr CG, Scott ML (1974) Antioxidant effects on selenium and vitamin E function in the chick. J Nutr 104(10):1297Google Scholar
  42. 42.
    Wang J, Liu Z, He X, Lian S, Liang J, Yu D, Sun D, Wu R (2018) Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway. Metallomics 10(10):1390–1400PubMedGoogle Scholar
  43. 43.
    Sun L, Huang J, Deng J, Lei X (2018) Avian selenogenome: response to dietary Se and vitamin E deficiency and supplementation. Poult Sci.
  44. 44.
    Taylor RM, Sunde RA (2017) Selenium requirements based on muscle and kidney selenoprotein enzyme activity and transcript expression in the turkey poult (Meleagris gallopavo). PLoS One 12(11):e0189001PubMedPubMedCentralGoogle Scholar
  45. 45.
    Yao H, Wu Q, Zhang Z, Zhang J, Li S, Huang J, Ren F, Xu S, Wang X, Lei X (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of Se-deficient chicks. J Nutr 143(5):613–619PubMedPubMedCentralGoogle Scholar
  46. 46.
    Kumar M, Bijo AJ, Baghel RS, Reddy CRK, Jha B (2012) Selenium and spermine alleviate cadmium induced toxicity in the red seaweed Gracilaria dura by regulating antioxidants and DNA methylation. Plant Physiol Biochem 51(2):129–138PubMedGoogle Scholar
  47. 47.
    Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9(16):2395–2402PubMedGoogle Scholar
  48. 48.
    Dagar V, Hutchison W, Muscat A, Krishnan A, Hoke D, Buckle A, Siswara P, Amor D, Mann J, Pinner J, Colley A, Wilson M, Sachdev R, McGillivray G, Edwards M, Kirk E, Collins F, Jones K, Taylor J, Hayes I, Thompson E, Barnett C, Haan E, Freckmann M, Turner A, White S, Kamien B, Ma A, Mackenzie F, Baynam G, Kiraly-Borri C, Field M, Dudding-Byth T, Algar E (2018) Genetic variation affecting DNA methylation and the human imprinting disorder, Beckwith-Wiedemann syndrome. Clin Epigenetics 10(1):114PubMedPubMedCentralGoogle Scholar
  49. 49.
    Li B, Lu W, Qu J, Ye L, Du G, Wan X (2018) Loss of exosomal miR-148b from cancer-associated fibroblasts promotes endometrial cancer cell invasion and cancer metastasis. J Cell Physiol 234(3):2943–2953PubMedGoogle Scholar
  50. 50.
    Tao H, Dai C, Ding J, Yang J, Ding X, Xu S, Shi K (2018) Epigenetic aberrations of miR-369-5p and DNMT3A control Patched1 signal pathway in cardiac fibrosis. Toxicology 410:182–192PubMedGoogle Scholar
  51. 51.
    Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (2002) Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis. Proc Natl Acad Sci U S A 99(15):10060–10065PubMedPubMedCentralGoogle Scholar
  52. 52.
    Girault I, Tozlu S, Lidereau R, Bièche I (2003) Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin Cancer Res 9(12):4415–4422PubMedGoogle Scholar
  53. 53.
    Loree J, Koturbash I, Kutanzi K, Baker M, Pogribny I, Kovalchuk O (2006) Radiation-induced molecular changes in rat mammary tissue: possible implications for radiation-induced carcinogenesis. Int J Radiat Biol 82(11):805–815PubMedGoogle Scholar
  54. 54.
    Xu L, Sun W, Jia A, Qiu L, Xiao B, Mu L, Li J, Zhang X, Wei Y, Peng C, Zhang D, Xiang X (2018) MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α. J Inflamm (Lond) 15:15Google Scholar
  55. 55.
    Cheng L, Tang Y, Chen X, Zhao L, Liu S, Ma Y, Wang N, Zhou K, Zhou J, Zhou M (2018) Deletion of MBD2 inhibits proliferation of chronic myeloid leukaemia blast phase cells. Cancer Biol Ther 19(8):676–686PubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Veterinary MedicineNortheast Agricultural UniversityHarbinPeople’s Republic of China
  2. 2.Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary MedicineNortheast Agricultural UniversityHarbinPeople’s Republic of China

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