Top

Current Nutrition Reports

Published in:

01-06-2019 | Epigenetics | Nutrition and Aging (Y Gu, Section Editor)

CpG and Non-CpG Methylation in the Diet–Epigenetics–Neurodegeneration Connection

Authors: Andrea Fuso, Marco Lucarelli

Published in: Current Nutrition Reports | Issue 2/2019

Abstract

Purpose of Review

Unraveling the diet–epigenetics–neurodegeneration connection may disclose associated mechanisms and novel approaches to the neurodegenerative diseases. This review summarizes the basic concepts and the innovative results in this field focusing on the relevance of non-CpG methylation.

Recent Findings

Many multifactorial neurodegenerative diseases are associated with epigenetic changes, and the brain seems more prone to epigenetic changes than other tissues. Several environmental factors induce epigenetic modulation in the organisms: diet and nutrition retain a high capacity to modulate the epigenetic traits. Finally, unexpected, specific, and functional non-CpG methylation in the brain was identified.

Summary

Non-CpG methylation modulates brain expression of genes especially in promoters characterized by low-density CpGs distribution. These genes appear more prone to the epigenetic effect of environmental factors, i.e., diet, possibly inducing neurodegenerative processes. Understanding these processes could help in setting nutritional intervention aimed at contrasting neurodegenerative diseases.

Skinner MK. Environmental epigenetics. Environ Epigenet. 2015;1:dvv002. https://doi.org/10.1093/eep/dvv002.CrossRefPubMedPubMedCentral

•• Fuso A. Aging and disease: the epigenetic bridge. In: Tollefsbol TO, editor. Epigenetic in human disease. 2nd ed: Elsevier; 2018. The whole book, at its second edition, offers a comprehensive review of the epigenetics determinant of human diseases.

Nicolia V, Lucarelli M, Fuso A. Environment, epigenetics and neurodegeneration: focus on nutrition in Alzheimer’s disease. Exp Gerontol. 2015;68:8–12. https://doi.org/10.1016/j.exger.2014.10.006.CrossRefPubMed

Romani M, Pistillo MP, Banelli B. Environmental epigenetics: crossroad between public health, lifestyle, and cancer prevention. Biomed Res Int. 2015;2015:587983–13. https://doi.org/10.1155/2015/587983.CrossRefPubMedPubMedCentral

• Deichmann U. Why epigenetics is not a vindication of Lamarckism—and why that matters. Stud Hist Philos Biol Biomed Sci. 2016;57:80–2. https://doi.org/10.1016/j.shpsc.2016.04.004 Acute dissertation on the implication of environmental epigenetics on the developmental and evolutionary theories.CrossRefPubMed

Penny D. Epigenetics, Darwin, and Lamarck. Genome Biol Evol. 2015;7:1758–60. https://doi.org/10.1093/gbe/evv107.CrossRefPubMedPubMedCentral

Skinner MK. Environmental epigenetics and a unified theory of the molecular aspects of evolution: a neo-Lamarckian concept that facilitates neo-Darwinian evolution. Genome Biol Evol. 2015;7:1296–302. https://doi.org/10.1093/gbe/evv073.CrossRefPubMedPubMedCentral

Tammen SA, Friso S, Choi SW. Epigenetics: the link between nature and nurture. Mol Aspects Med. 201334:753–64. https://doi.org/10.1016/j.mam.2012.07.018.

Alegría-Torres JA, Baccarelli A, Bollati V. Epigenetics and lifestyle. Epigenomics. 2011;3:267–77. https://doi.org/10.2217/epi.11.22.CrossRefPubMedPubMedCentral

10.

Champagne FA. Epigenetic legacy of parental experiences: dynamic and interactive pathways to inheritance. Dev Psychopathol. 2016;28:1219–28.CrossRef

11.

Meloni M, Müller R. Transgenerational epigenetic inheritance and social responsibility: perspectives from the social sciences. Environ Epigenet. 2018;4:dvy019. https://doi.org/10.1093/eep/dvy019.CrossRefPubMedPubMedCentral

12.

Dominguez-Salas P, Moore SE, Baker MS, Bergen AW, Cox SE, Dyer RA, et al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014;5:3746. https://doi.org/10.1038/ncomms4746.CrossRefPubMedPubMedCentral

13.

Soubry A, Hoyo C, Jirtle RL, Murphy SK. A paternal environmental legacy: evidence for epigenetic inheritance through the male germ line. Bioessays. 2014;36:359–71. https://doi.org/10.1002/bies.201300113.CrossRefPubMedPubMedCentral

14.

Burdge GC, Hoile SP, Uller T, Thomas NA, Gluckman PD, Hanson MA, et al. Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition. PLoS One. 2011;6:e28282. https://doi.org/10.1371/journal.pone.0028282.CrossRefPubMedPubMedCentral

15.

Weyrich A, Jeschek M, Schrapers KT, Lenz D, Chung TH, Rübensam K, et al. Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs. Environ Epigenet. 2018;4:dvy011. https://doi.org/10.1093/eep/dvy011.CrossRefPubMedPubMedCentral

16.

Nilsson EE, Sadler-Riggleman I, Skinner MK. Environmentally induced epigenetic transgenerational inheritance of disease. Environ Epigenet. 2018;4(2):dvy016. https://doi.org/10.1093/eep/dvy016.CrossRefPubMedPubMedCentral

17.

Li X, Shi X, Hou Y, Cao X, Gong L, Wang H, et al. Paternal hyperglycemia induces transgenerational inheritance of susceptibility to hepatic steatosis in rats involving altered methylation on Pparα promoter. Biochim Biophys Acta Mol basis Dis. 1865;2019:147–60. https://doi.org/10.1016/j.bbadis.2018.10.040.CrossRef

18.

Tiffon C. The impact of nutrition and environmental epigenetics on human health and disease. Int J Mol Sci. 2018;19:E3425. https://doi.org/10.3390/ijms19113425.CrossRefPubMed

19.

Keil KP, Lein PJ. DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? Environ Epigenet. 2016:dvv012.

20.

Kubota T. Epigenetic alterations induced by environmental stress associated with metabolic and neurodevelopmental disorders. Environ Epigenet. 2016;2:dvw017. https://doi.org/10.1093/eep/dvw017.CrossRefPubMedPubMedCentral

21.

Hack LM, Dick ALW, Provençal N. Epigenetic mechanisms involved in the effects of stress exposure: focus on 5-hydroxymethylcytosine. Environ Epigenet. 2016;2:dvw016. https://doi.org/10.1093/eep/dvw016.CrossRefPubMedPubMedCentral

22.

Keller SM, Roth TL. Environmental influences on the female epigenome and behavior. Environ Epigenet. 2016;2:dvw007.CrossRef

23.

Zhang X, Chen X, Weirauch MT, Zhang X, Burleson JD, Brandt EB, et al. Diesel exhaust and house dust mite allergen lead to common changes in the airway methylome and hydroxymethylome. Environ Epigenet. 2018;4:dvy020. https://doi.org/10.1093/eep/dvy020.CrossRefPubMedPubMedCentral

24.

Kochmanski J, Marchlewicz EH, Dolinoy DC. Longitudinal effects of developmental bisphenol A, variable diet, and physical activity on age-related methylation in blood. Environ Epigenet. 2018;4:dvy017. https://doi.org/10.1093/eep/dvy017.CrossRefPubMedPubMedCentral

25.

Strakovsky RS, Schantz SL. Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta. Environ Epigenet. 2018;4:dvy022. https://doi.org/10.1093/eep/dvy022.CrossRefPubMedPubMedCentral

26.

Burris HH, Baccarelli AA, Byun HM, Cantoral A, Just AC, Pantic I, et al. Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight. Epigenetics. 2015;10:913–21. https://doi.org/10.1080/15592294.2015.1078963.CrossRefPubMedPubMedCentral

27.

Lin VW, Baccarelli AA, Burris HH. Epigenetics-a potential mediator between air pollution and preterm birth. Environ Epigenet. 2016;2. https://doi.org/10.1093/eep/dvv008.

28.

Thorsell A, Nätt D. Maternal stress and diet may influence affective behavior and stress-response in offspring via epigenetic regulation of central peptidergic function. Environ Epigenet. 2016;2:dvw012. https://doi.org/10.1093/eep/dvw012.CrossRefPubMedPubMedCentral

29.

Bozack AK, Cardenas A, Quamruzzaman Q, Rahman M, Mostofa G, Christiani DC, et al. DNA methylation in cord blood as mediator of the association between prenatal arsenic exposure and gestational age. Epigenetics. 2018;13:923–40. https://doi.org/10.1080/15592294.2018.1516453.CrossRefPubMed

30.

Goodrich JM, Dolinoy DC, Sánchez BN, Zhang Z, Meeker JD, Mercado-Garcia A, et al. Adolescent epigenetic profiles and environmental exposures from early life through peri-adolescence. Environ Epigenet. 2016;2:dvw018. https://doi.org/10.1093/eep/dvw018.CrossRefPubMedPubMedCentral

31.

Gonzalo S. Epigenetic alterations in aging. J Appl Physiol. 2010;109:586–97.CrossRef

32.

Thompson RF, Einstein FH. Epigenetic basis for fetal origins of age-related disease. J Womens Health (Larchmt). 2010;19:581–7.CrossRef

33.

Quach A, Levine ME, Tanaka T, Lu AT, Chen BH, Ferrucci L, et al. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging (Albany NY). 2017;9:419–46. https://doi.org/10.18632/aging.101168.CrossRef

34.

Grau-Perez M, Agha G, Pang Y, Bermudez JD, Tellez-Plaza M. Mendelian randomization and the environmental epigenetics of health: a systematic review. Curr Environ Health Rep. 2019. https://doi.org/10.1007/s40572-019-0226-3.

35.

Watson RE, Goodman JI. Epigenetics and DNA methylation come of age in toxicology. Toxicol Sci. 2002;67:11–6.CrossRef

36.

Ingelman-Sundberg M, Zhong XB, Hankinson O, Beedanagari S, Yu AM, Peng L, et al. Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab Dispos. 2013;41:1725–31. https://doi.org/10.1124/dmd.113.053157.CrossRefPubMedPubMedCentral

37.

• Martin EM, Fry RC. Environmental influences on the epigenome: exposure-associated DNA methylation in human populations. Annu Rev Public Health. 2018;39:309–33. https://doi.org/10.1146/annurev-publhealth-040617-014629 Review on epidemiological relevance of environmental epigenetics.CrossRefPubMed

38.

Huang W, Zhao C, Zhong H, Zhang S, Xia Y, Cai Z. Bisphenol S induced epigenetic and transcriptional changes in human breast cancer cell line MCF-7. Environ Pollut. 2019;246:697–703. https://doi.org/10.1016/j.envpol.2018.12.084.CrossRefPubMed

39.

Drobná Z, Henriksen AD, Wolstenholme JT, Montiel C, Lambeth PS, Shang S, et al. Transgenerational effects of bisphenol a on gene expression and DNA methylation of imprinted genes in brain. Endocrinology. 2018;159:132–44. https://doi.org/10.1210/en.2017-00730.CrossRefPubMed

40.

Kwiatkowska M, Reszka E, Woźniak K, Jabłońska E, Michałowicz J, Bukowska B. DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem Toxicol. 2017;105:93–8. https://doi.org/10.1016/j.fct.2017.03.051.CrossRefPubMed

41.

•• Stover PJ, James WPT, Krook A, Garza C. Emerging concepts on the role of epigenetics in the relationships between nutrition and health. J Intern Med. 2018;284:37–49. https://doi.org/10.1111/joim.12768 Reviews the nutrition factors inducing epigenetic changes.CrossRefPubMed

42.

Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res. 2015;116:715–36. https://doi.org/10.1161/CIRCRESAHA.116.303936.CrossRefPubMed

43.

Chiu S, Woodbury-Fariña MA, Shad MU, Husni M, Copen J, Bureau Y, et al. The role of nutrient-based epigenetic changes in buffering against stress, aging, and Alzheimer’s disease. Psychiatr Clin North Am. 2014;37:591–623. https://doi.org/10.1016/j.psc.2014.09.001.CrossRefPubMed

44.

Kanherkar RR, Bhatia-Dey N, Csoka AB. Epigenetics across the human lifespan. Front Cell Dev Biol. 2014;2:49. https://doi.org/10.3389/fcell.2014.00049.CrossRefPubMedPubMedCentral

45.

Lillycrop KA, Burdge GC. Maternal diet as a modifier of offspring epigenetics. J Dev Orig Health Dis. 2015;6:88–95. https://doi.org/10.1017/S2040174415000124.CrossRefPubMed

46.

Vickers MH. Early life nutrition, epigenetics and programming of later life disease. Nutrients. 2014;6:2165–78. https://doi.org/10.3390/nu6062165.CrossRefPubMedPubMedCentral

47.

Saffery R, Novakovic B. Epigenetics as the mediator of fetal programming of adult onset disease: what is the evidence? Acta Obstet Gynecol Scand. 2014;93:1090–8. https://doi.org/10.1111/aogs.12431.CrossRefPubMed

48.

Paul B, Barnes S, Demark-Wahnefried W, Morrow C, Salvador C, Skibola C, et al. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clin Epigenetics. 2015;7:112. https://doi.org/10.1186/s13148-015-0144-7.CrossRefPubMedPubMedCentral

49.

Hullar MA, Fu BC. Diet, the gut microbiome, and epigenetics. Cancer J. 2014;20:170–5. https://doi.org/10.1097/PPO.0000000000000053.CrossRefPubMedPubMedCentral

50.

Rasool M, Malik A, Naseer MI, Manan A, Ansari S, Begum I, et al. The role of epigenetics in personalized medicine: challenges and opportunities. BMC Med Genomics. 2015;8(Suppl 1):S5. https://doi.org/10.1186/1755-8794-8-S1-S5.CrossRefPubMedPubMedCentral

51.

• Majchrzak-Celińska A, Baer-Dubowska W. Pharmacoepigenetics: an element of personalized therapy? Expert Opin Drug Metab Toxicol. 2017;13:387–98. https://doi.org/10.1080/17425255.2017.1260546 Interesting perspectives on the epigenetic therapies in the frameshift of personalized medicine.CrossRefPubMed

52.

•• Huang D, Cui L, Ahmed S, Zainab F, Wu Q, Wang X, et al. An overview of epigenetic agents and natural nutrition products targeting DNA methyltransferase, histone deacetylases and microRNAs. Food Chem Toxicol. 2019;123:574–94. https://doi.org/10.1016/j.fct.2018.10.052 A comprehensive review of the nutritional factors affecting epigenetic traits.CrossRefPubMed

53.

Fu LJ, Ding YB, Wu LX, Wen CJ, Qu Q, Zhang X, et al. The effects of lycopene on the methylation of the GSTP1 promoter and global methylation in prostatic cancer cell lines PC3 and LNCaP. Int J Endocrinol. 2014;2014:620165–9. https://doi.org/10.1155/2014/620165.CrossRefPubMedPubMedCentral

54.

Fernández-Bedmar Z, Anter J, Alonso-Moraga A, Martín de las Mulas J, Millán-Ruiz Y, Guil-Luna S. Demethylating and anti-hepatocarcinogenic potential of hesperidin, a natural polyphenol of citrus juices. Mol Carcinog. 2017;56:1653–62. https://doi.org/10.1002/mc.22621.CrossRefPubMed

55.

Li Y, Chen F, Wei A, Bi F, Zhu X, Yin S, et al. Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice. J Mol Med (Berl). 2019. https://doi.org/10.1007/s00109-019-01759-z.

56.

Romagnolo DF, Donovan MG, Papoutsis AJ, Doetschman TC, Selmin OI. Genistein prevents BRCA1 CpG methylation and proliferation in human breast cancer cells with activated aromatic hydrocarbon receptor. Curr Dev Nutr. 2017;1:e000562. https://doi.org/10.3945/cdn.117.000562.CrossRefPubMedPubMedCentral

57.

Weng YP, Hung PF, Ku WY, Chang CY, Wu BH, Wu MH, et al. The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers. Oncotarget. 2017;9(1):361–74. https://doi.org/10.18632/oncotarget.23015.CrossRefPubMedPubMedCentral

58.

Gianfredi V, Nucci D, Vannini S, Villarini M, Moretti M. In vitro biological effects of Sulforaphane (SFN), epigallocatechin-3-gallate (EGCG), and curcumin on breast cancer cells: a systematic review of the literature. Nutr Cancer. 2017;69:969–78. https://doi.org/10.1080/01635581.2017.1359322.CrossRefPubMed

59.

Morris J, Moseley VR, Cabang AB, Coleman K, Wei W, Garrett-Mayer E, et al. Reduction in promotor methylation utilizing EGCG (epigallocatechin-3-gallate) restores RXRα expression in human colon cancer cells. Oncotarget. 2016;7(23):35313–26. https://doi.org/10.18632/oncotarget.9204.CrossRefPubMedPubMedCentral

60.

Lewinska A, Adamczyk-Grochala J, Deregowska A, Wnuk M. Sulforaphane-induced cell cycle arrest and senescence are accompanied by DNA hypomethylation and changes in microRNA profile in breast cancer cells. Theranostics. 2017;7:3461–77. https://doi.org/10.7150/thno.20657.CrossRefPubMedPubMedCentral

61.

Boyanapalli SS, Li W, Fuentes F, Guo Y, Ramirez CN, Gonzalez XP, et al. Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells. Pharmacol Res. 2016;114:175–84. https://doi.org/10.1016/j.phrs.2016.10.021.CrossRefPubMedPubMedCentral

62.

Kaufman-Szymczyk A, Majewski G, Lubecka-Pietruszewska K, Fabianowska-Majewska K. The role of sulforaphane in epigenetic mechanisms, including interdependence between histone modification and DNA methylation. Int J Mol Sci. 2015;16:29732–43. https://doi.org/10.3390/ijms161226195.CrossRefPubMedPubMedCentral

63.

Chen J, Ying Y, Zhu H, Zhu T, Qu C, Jiang J, et al. Curcumin-induced promoter hypermethylation of the mammalian target of rapamycin gene in multiple myeloma cells. Oncol Lett. 2019;17:1108–14. https://doi.org/10.3892/ol.2018.9662.CrossRefPubMed

64.

Chatterjee B, Ghosh K, Kanade SR. Curcumin-mediated demethylation of the proximal promoter CpG island enhances the KLF4 recruitment that leads to increased expression of p21Cip1 in vitro. J Cell Biochem. 2019;120:809–20. https://doi.org/10.1002/jcb.27442.CrossRefPubMed

65.

Maugeri A, Mazzone MG, Giuliano F, Vinciguerra M, Basile G, Barchitta M, et al. Curcumin modulates DNA methyltransferase functions in a cellular model of diabetic retinopathy. Oxidative Med Cell Longev. 2018;2018:5407482–12. https://doi.org/10.1155/2018/5407482.CrossRef

66.

Hassan HE, Carlson S, Abdallah I, Buttolph T, Glass KC, Fandy TE. Curcumin and dimethoxycurcumin induced epigenetic changes in leukemia cells. Pharm Res. 2015;32:863–75. https://doi.org/10.1007/s11095-014-1502-4.CrossRefPubMed

67.

Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S. Emerging role of epigenetics in the actions of alcohol. Alcohol Clin Exp Res. 2008;32:1525–34. https://doi.org/10.1111/j.1530-0277.2008.00729.x.CrossRefPubMed

68.

Li Y, Daniel M, Tollefsbol TO. Epigenetic regulation of caloric restriction in aging. BMC Med. 2011;9:98. https://doi.org/10.1186/1741-7015-9-98.CrossRefPubMedPubMedCentral

69.

Hahn O, Grönke S, Stubbs TM, Ficz G, Hendrich O, Krueger F, et al. Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism. Genome Biol. 2017;18:56. https://doi.org/10.1186/s13059-017-1187-1.CrossRefPubMedPubMedCentral

70.

Hadad N, Unnikrishnan A, Jackson JA, Masser DR, Otalora L, Stanford DR, et al. Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation. Neurobiol Aging. 2018;67:53–66. https://doi.org/10.1016/j.neurobiolaging.2018.03.009.CrossRefPubMed

71.

Yoon A, Tammen SA, Park S, Han SN, Choi SW. Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice. Nutr Res Pract. 2017;11:105–13. https://doi.org/10.4162/nrp.2017.11.2.105.CrossRefPubMedPubMedCentral

72.

Boddicker RL, Koltes JE, Fritz-Waters ER, Koesterke L, Weeks N, Yin T, et al. Genome-wide methylation profile following prenatal and postnatal dietary omega-3 fatty acid supplementation in pigs. Anim Genet. 2016;47:658–71. https://doi.org/10.1111/age.12468.CrossRefPubMed

73.

Lai CQ, Wojczynski MK, Parnell LD, Hidalgo BA, Irvin MR, Aslibekyan S, et al. Epigenome-wide association study of triglyceride postprandial responses to a high-fat dietary challenge. J Lipid Res. 2016;57:2200–7.CrossRef

74.

Finkelstein JD. Homocysteine: a history in progress. Nutr Rev. 2000;58:193–204.CrossRef

75.

Fuso A, Nicolia V, Ricceri L, Cavallaro RA, Isopi E, Mangia F, et al. S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging. 2012;33:1482.e1–16. https://doi.org/10.1016/j.neurobiolaging.2011.12.013.CrossRef

76.

Ulrey CL, Liu L, Andrews LG, Tollefsbol TO. The impact of metabolism on DNA methylation. Hum Mol Genet. 2005;14:R139–47.CrossRef

77.

Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health and disease. J Exp Med. 2019;216:253–66. https://doi.org/10.1084/jem.20181965.CrossRefPubMed

78.

Pieroth R, Paver S, Day S, Lammersfeld C. Folate and its impact on cancer risk. Curr Nutr Rep. 2018;7:70–84. https://doi.org/10.1007/s13668-018-0237-y.CrossRefPubMedPubMedCentral

79.

Fuso A. The ‘golden age’ of DNA methylation in neurodegenerative diseases. Clin Chem Lab Med. 2013;51:523–34. https://doi.org/10.1515/cclm-2012-0618.CrossRefPubMed

80.

Neal M, Richardson JR. Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration. Biochim Biophys Acta Mol basis Dis. 1864;2018:432–43. https://doi.org/10.1016/j.bbadis.2017.11.004.CrossRef

81.

Gao J, Cahill CM, Huang X, Roffman JL, Lamon-Fava S, Fava M, et al. S-Adenosyl methionine and transmethylation pathways in neuropsychiatric diseases throughout life. Neurotherapeutics. 2018;15:156–75. https://doi.org/10.1007/s13311-017-0593-0.CrossRefPubMedPubMedCentral

82.

Dolinar A, Ravnik-Glavač M, Glavač D. Epigenetic mechanisms in amyotrophic lateral sclerosis: a short review. Mech Ageing Dev. 2018;174:103–10. https://doi.org/10.1016/j.mad.2018.03.005.CrossRefPubMed

83.

Maltby VE, Lea RA, Graves MC, Sanders KA, Benton MC, Tajouri L, et al. Genome-wide DNA methylation changes in CD19(+) B cells from relapsing-remitting multiple sclerosis patients. Sci Rep. 2018;8:17418. https://doi.org/10.1038/s41598-018-35603-0.CrossRefPubMedPubMedCentral

84.

Smith RG, Lunnon K. DNA modifications and Alzheimer’s disease. Adv Exp Med Biol. 2017;978:303–19. https://doi.org/10.1007/978-3-319-53889-1_16.CrossRefPubMed

85.

Feng Y, Jankovic J, Wu YC. Epigenetic mechanisms in Parkinson’s disease. J Neurol Sci. 2015;349:3–9. https://doi.org/10.1016/j.jns.2014.12.017.CrossRefPubMed

86.

Athanasopoulos D, Karagiannis G, Tsolaki M. Recent findings in Alzheimer disease and nutrition focusing on epigenetics. Adv Nutr. 2016;7:917–27. https://doi.org/10.3945/an.116.012229.CrossRefPubMedPubMedCentral

87.

Fuso A, Nicolia V, Cavallaro RA, Scarpa S. DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimer’s disease models. J Nutr Biochem. 2011;22:242–51. https://doi.org/10.1016/j.jnutbio.2010.01.010.CrossRefPubMed

88.

Fuso A, Nicolia V, Pasqualato A, Fiorenza MT, Cavallaro RA, Scarpa S. Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency. Neurobiol Aging. 2011;32:187–99. https://doi.org/10.1016/j.neurobiolaging.2009.02.013.CrossRefPubMed

89.

Edwards JR, Yarychkivska O, Boulard M, Bestor TH. DNA methylation and DNA methyltransferases. Epigenetics Chromatin. 2017;10:23. https://doi.org/10.1186/s13072-017-0130-8.CrossRefPubMedPubMedCentral

90.

Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18:517–34. https://doi.org/10.1038/nrg.2017.33.CrossRef

91.

Fouse SD, Nagarajan RO, Costello JF. Genome-scale DNA methylation analysis. Epigenomics. 2010;2:105–17.CrossRef

92.

Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B, et al. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci. 2014;17:215–22. https://doi.org/10.1038/nn.3607.CrossRefPubMed

93.

Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013;341:1237905. https://doi.org/10.1126/science.1237905.CrossRefPubMedPubMedCentral

94.

• Jang HS, Shin WJ, Lee JE, Do JT. CpG and non-CpG methylation in epigenetic gene regulation and brain function. Genes (Basel). 2017;8(6):E148. https://doi.org/10.3390/genes8060148 Clear explanation on the functional role of non-CpG methylation.CrossRef

95.

Fuso A, Scarpa S, Grandoni F, Strom R, Lucarelli M. A reassessment of semiquantitative analytical procedures for DNA methylation: comparison of bisulfite- and HpaII polymerase-chain-reaction-based methods. Anal Biochem. 2006;350:24–31.CrossRef

96.

Fuso A, Ferraguti G, Grandoni F, Ruggeri R, Scarpa S, Strom R, et al. Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region: a priming effect on the spreading of active demethylation. Cell Cycle. 2010;9:3965–76.CrossRef

97.

•• Fuso A, Ferraguti G, Scarpa S, Ferrer I, Lucarelli M. Disclosing bias in bisulfite assay: MethPrimers underestimate high DNA methylation. PLoS One. 2015;10:e0118318. https://doi.org/10.1371/journal.pone.0118318 Evidence a technical bias on bisulfite assay.CrossRefPubMedPubMedCentral

98.

Nicolia V, Cavallaro RA, López-González I, Maccarrone M, Scarpa S, Ferrer I, et al. DNA methylation profiles of selected pro-inflammatory cytokines in Alzheimer disease. J Neuropathol Exp Neurol. 2017;76:27–31. https://doi.org/10.1093/jnen/nlw099.CrossRefPubMed

99.

Illingworth RS, Bird AP. CpG islands—‘a rough guide’. FEBS Lett. 2009;583:1713–20. https://doi.org/10.1016/j.febslet.2009.04.012.CrossRefPubMed

100.

Kozlenkov A, Roussos P, Timashpolsky A, Barbu M, Rudchenko S, Bibikova M, et al. Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites. Nucleic Acids Res. 2014;42:109–27. https://doi.org/10.1093/nar/gkt838.CrossRefPubMed

101.

Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, et al. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc Natl Acad Sci U S A. 2015;112:5509–14. https://doi.org/10.1073/pnas.1505909112.CrossRefPubMedPubMedCentral

102.

Kinde B, Gabel HW, Gilbert CS, Griffith EC, Greenberg ME. Reading the unique DNA methylation landscape of the brain: non-CpG methylation, hydroxymethylation, and MeCP2. Proc Natl Acad Sci U S A. 2015;112(22):6800–6. https://doi.org/10.1073/pnas.1411269112.CrossRefPubMedPubMedCentral

103.

Pietrzak M, Rempala GA, Nelson PT, Hetman M. Non-random distribution of methyl-CpG sites and non-CpG methylation in the human rDNA promoter identified by next generation bisulfite sequencing. Gene. 2016;585:35–43. https://doi.org/10.1016/j.gene.2016.03.028.CrossRefPubMedPubMedCentral

104.

Fuso A, Iyer AM, van Scheppingen J, Maccarrone M, Scholl T, Hainfellner JA, et al. Promoter-specific hypomethylation correlates with IL-1β overexpression in tuberous sclerosis complex (TSC). J Mol Neurosci. 2016;59:464–70. https://doi.org/10.1007/s12031-016-0750-7.CrossRefPubMedPubMedCentral

105.

Lee JH, Park SJ, Nakai K. Differential landscape of non-CpG methylation in embryonic stem cells and neurons caused by DNMT3s. Sci Rep. 2017;7:11295. https://doi.org/10.1038/s41598-017-11800-1.CrossRefPubMedPubMedCentral

106.

Keller S, Punzo D, Cuomo M, Affinito O, Coretti L, Sacchi S, et al. DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia. Sci Rep. 2018;8:10163. https://doi.org/10.1038/s41598-018-28332-x.CrossRefPubMedPubMedCentral

107.

Rizzardi LF, Hickey PF, Rodriguez DiBlasi V, Tryggvadóttir R, Callahan CM, Idrizi A, et al. Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability. Nat Neurosci. 2019;22:307–16. https://doi.org/10.1038/s41593-018-0297-8.CrossRefPubMed

Title: CpG and Non-CpG Methylation in the Diet–Epigenetics–Neurodegeneration Connection
Authors: Andrea Fuso
Marco Lucarelli
Publication date: 01-06-2019
Publisher: Springer US
Keyword: Epigenetics
Published in: Current Nutrition Reports / Issue 2/2019
Electronic ISSN: 2161-3311
DOI: https://doi.org/10.1007/s13668-019-0266-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

CpG and Non-CpG Methylation in the Diet–Epigenetics–Neurodegeneration Connection

Abstract

Purpose of Review

Recent Findings

Summary

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content

Other articles of this Issue 2/2019

Brain Imaging of Taste Perception in Obesity: a Review

Impact of Brain Insulin Signaling on Dopamine Function, Food Intake, Reward, and Emotional Behavior

Excessive Consumption of Sugar: an Insatiable Drive for Reward

Drug-Nutrition Interactions and the Brain: It’s Not All in Your Head

Brazilian Children’s Dietary Intake in Relation to Brazil’s New Nutrition Guidelines: a Systematic Review

Prebiotic Intake in Older Adults: Effects on Brain Function and Behavior

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page