Skip to main content
SpringerLink
Log in

Epigenetics: At the Crossroads Between Genetic and Environmental Determinants of Disease

  • Chapter
  • First Online:
Bone Health

  • 528 Accesses

Abstract

Epigenetic modifications play an essential role in the functional regulation of genes, including their expression. In contrast to the relative stability of the genome, the epigenome varies in a very dynamic way, through what are known as epigenetic mechanisms. These epigenetic modifications are reversible and are conditioned by environmental pressures. The most well-known epigenetic DNA modifications are the methylation of the cytosines present in the context of cytosine-guanine dinucleotides and the posttranslational modification of histones. Several works have reported that events in the early environment are associated with changes in gene expression and biological function and that such changes persist beyond the immediate influence of the stimulus and into adulthood. While the exact molecular mechanisms underlying developmental programming are largely unknown, there is much epidemiological evidence and data from animal studies linking epigenetic modifications with parental lifestyle (e.g., alcohol or tobacco consumption), nutrition, and environmental factors (such as exposure to UV light or heavy metals and stress). Moreover, pre-existing pathologies in the parents (e.g., diabetes, obesity, or metabolic syndrome) can also increase the susceptibility of the offspring to developing certain diseases over the course of their lifetime.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Waddington CH. The epigenotype. Int J Epidemiol. 2012;41(1):10–3. https://doi.org/10.1093/ije/dyr184.

    Article  CAS  PubMed  Google Scholar 

  2. Ecker S, Pancaldi V, Valencia A, Beck S, Paul DS. Epigenetic and transcriptional variability shape phenotypic plasticity. Bioessays. 2018;40(2):1700148. https://doi.org/10.1002/bies.201700148.

    Article  CAS  Google Scholar 

  3. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447(7143):425–32. https://doi.org/10.1038/nature05918.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 2007;8(4):286–98. https://doi.org/10.1038/nrg2005.

    Article  CAS  PubMed  Google Scholar 

  6. Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet. 2007;23(8):413–8. https://doi.org/10.1016/j.tig.2007.05.008.

    Article  CAS  PubMed  Google Scholar 

  7. Kulis M, Queirós AC, Beekman R, Martín-Subero JI. Intragenic DNA methylation in transcriptional regulation, normal differentiation and cancer. Biochim Biophy Acta. 2013;1829(11):1161–74. https://doi.org/10.1016/j.bbagrm.2013.08.001.

    Article  CAS  Google Scholar 

  8. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science. 2001;293(5532):1068–70. https://doi.org/10.1126/science.1063852.

    Article  CAS  PubMed  Google Scholar 

  9. Jjingo D, Conley AB, Soojin VY, Lunyak VV, Jordan IK. On the presence and role of human gene-body DNA methylation. Oncotarget. 2012;3(4):462. https://doi.org/10.18632/oncotarget.497.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Subramaniam D, Thombre R, Dhar A, Anant S. DNA methyltransferases: a novel target for prevention and therapy. Front Oncol. 2014;4:80. https://doi.org/10.3389/fonc.2014.00080.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gowher H, Jeltsch A. Mammalian DNA methyltransferases: new discoveries and open questions. Biochem Soc Trans. 2018;46(5):1191–202. https://doi.org/10.1042/BST20170574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wyatt GR, Cohen SS. A new pyrimidine base from bacteriophage nucleic acids. Nature. 1952;170(4338):1072.

    Article  CAS  PubMed  Google Scholar 

  13. Penn NW, Suwalski R, O’riley C, Bojanowski K, Yura R. The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid. Biochem J. 1972;126(4):781–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929–30. https://doi.org/10.1126/science.1169786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5. https://doi.org/10.1126/science.1170116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. López V, Fernández AF, Fraga MF. The role of 5-hydroxymethylcytosine in development, aging and age-related diseases. Ageing Res Rev. 2017;37:28–38. https://doi.org/10.1016/j.arr.2017.05.002.

    Article  CAS  PubMed  Google Scholar 

  17. He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303–7. https://doi.org/10.1126/science.1210944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, Ibberson D, Barath P, Demay F, Reid G, Benes V, Jeltsch A, Gannon F, Salbert G. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008;452(7183):45–50. https://doi.org/10.1038/nature06544.

    Article  CAS  PubMed  Google Scholar 

  19. Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18(9):517. https://doi.org/10.1038/nrg.2017.33.

    Article  CAS  PubMed  Google Scholar 

  20. Branco MR, Ficz G, Reik W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13(1):7. https://doi.org/10.1038/nrg3080.

    Article  CAS  Google Scholar 

  21. Globisch D, Münzel M, Müller M, Michalakis S, Wagner M, Koch S, Brückl T, Biel M, Carell T. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One. 2010;5(12):e15367. https://doi.org/10.1371/journal.pone.0015367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huh YH, Cohen J, Sherley JL. Higher 5-hydroxymethylcytosine identifies immortal DNA strand chromosomes in asymmetrically self-renewing distributed stem cells. Proc Natl Acad Sci U S A. 2013;110(42):16862–7. https://doi.org/10.1073/pnas.1310323110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shen L, Zhang Y. 5-hydroxymethylcytosine: generation, fate, and genomic distribution. Curr Opin Cell Biol. 2013;25(3):289–96. https://doi.org/10.1016/j.ceb.2013.02.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kriaucionis S, Tahiliani M. Expanding the epigenetic landscape: novel modifications of cytosine in genomic DNA. Cold Spring Harb Perspect Biol. 2014;6(10):a018630. https://doi.org/10.1101/cshperspect.a018630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Laird A, Thomson JP, Harrison DJ, Meehan RR. 5-Hydroxymethylcytosine profiling as an indicator of cellular state. Epigenomics. 2013;5(6):655–69. https://doi.org/10.2217/epi.13.69.

    Article  CAS  PubMed  Google Scholar 

  26. Guo JU, Szulwach KE, Su Y, Li Y, Yao B, Xu Z, Shin JH, Xie B, Gao Y, Ming GL, Jin P. Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the adult mouse brain. Front Biol (Beijing). 2014;9(1):66–74. https://doi.org/10.1007/s11515-014-1295-1.

    Article  CAS  Google Scholar 

  27. Jin SG, Jiang Y, Qiu R, Rauch TA, Wang Y, Schackert G, Krex D, Lu Q, Pfeifer GP. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res. 2011;71(24):7360–5. https://doi.org/10.1158/0008-5472.CAN-11-2023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wen L, Tang F. Genomic distribution and possible functions of DNA hydroxymethylation in the brain. Genomics. 2014;104(5):341–6. https://doi.org/10.1016/j.ygeno.2014.08.020.

    Article  CAS  PubMed  Google Scholar 

  29. Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA, Marques CJ, Andrews S, Reik W. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature. 2011;473(7347):398–402. https://doi.org/10.1038/nature10008.

    Article  CAS  PubMed  Google Scholar 

  30. Stroud H, Feng S, Kinney SM, Pradhan S, Jacobsen SE. 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol. 2011;12(6):R54. https://doi.org/10.1186/gb-2011-12-6-r54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151(7):1417–30. https://doi.org/10.1016/j.cell.2012.11.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kimura H, Cook PR. Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J Cell Biol. 2001;153(7):1341–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wyrick JJ, Parra MA. The role of histone H2A and H2B post-translational modifications in transcription: a genomic perspective. Biochim Biophys Acta. 2009;1789(1):37–44. https://doi.org/10.1016/j.bbagrm.2008.07.001.

    Article  CAS  PubMed  Google Scholar 

  34. Parra MA, Kerr D, Fahy D, Pouchnik DJ, Wyrick JJ. Deciphering the roles of the histone H2B N-terminal domain in genome-wide transcription. Mol Cell Biol. 2006;26(10):3842–52. https://doi.org/10.1128/MCB.26.10.3842-3852.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Parra MA, Wyrick JJ. Regulation of gene transcription by the histone H2A N-terminal domain. Mol Cell Biol. 2007;27(21):7641–8. https://doi.org/10.1128/MCB.00742-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bach SV, Hegde AN. The proteasome and epigenetics: zooming in on histone modifications. Biomol Concepts. 2016;7(4):215–27. https://doi.org/10.1515/bmc-2016-0016.

    Article  CAS  PubMed  Google Scholar 

  37. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–95. https://doi.org/10.1038/cr.2011.22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mariño-Ramírez L, Jordan IK, Landsman D. Multiple independent evolutionary solutions to core histone gene regulation. Genome Biol. 2006;7(12):R122. https://doi.org/10.1186/gb-2006-7-12-r122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705. https://doi.org/10.1016/j.cell.2007.02.005.

    Article  CAS  PubMed  Google Scholar 

  40. Smith ER, Cayrou C, Huang R, Lane WS, Côté J, Lucchesi JC. A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16. Mol Cell Biol. 2005;25(21):9175–88. https://doi.org/10.1128/MCB.25.21.9175-9188.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 2005;6(11):838–49. https://doi.org/10.1038/nrm1761.

    Article  CAS  PubMed  Google Scholar 

  42. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128(4):707–19. https://doi.org/10.1016/j.cell.2007.01.015.

    Article  CAS  PubMed  Google Scholar 

  43. Simon RP, Robaa D, Alhalabi Z, Sippl W, Jung M. KATching-up on small molecule modulators of lysine acetyltransferases. J Med Chem. 2016;59(4):1249–70. https://doi.org/10.1021/acs.jmedchem.5b01502.

    Article  CAS  PubMed  Google Scholar 

  44. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81–120. https://doi.org/10.1146/annurev.biochem.70.1.81.

    Article  CAS  PubMed  Google Scholar 

  45. Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev. 2000;64(2):435–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Su J, Wang F, Cai Y, Jin J. The functional analysis of histone acetyltransferase MOF in tumorigenesis. Int J Mol Sci. 2016;17(1):E99. https://doi.org/10.3390/ijms17010099.

    Article  CAS  PubMed  Google Scholar 

  47. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell. 2004;16(1):93–105. https://doi.org/10.1016/j.molcel.2004.08.031.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang R, Erler J, Langowski J. Histone acetylation regulates chromatin accessibility: role of H4K16 in inter-nucleosome interaction. Biophys J. 2017;112(3):450–9. https://doi.org/10.1016/j.bpj.2016.11.015.

    Article  CAS  PubMed  Google Scholar 

  49. Fraga MF, Ballestar E, Villar-Garea A, Boix-Chornet M, Espada J, Schotta G, Bonaldi T, Haydon C, Ropero S, Petrie K, Iyer NG. 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. https://doi.org/10.1038/ng1531.

    Article  CAS  PubMed  Google Scholar 

  50. Teperino R, Schoonjans K, Auwerx J. Histone methyl transferases and demethylases; can they link metabolism and transcription? Cell Metab. 2010;12(4):321–7. https://doi.org/10.1016/j.cmet.2010.09.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gavrilov AA, Razin SV. Compartmentalization of the cell nucleus and spatial organization of the genome. Mol Biol (Mosk). 2015;49(1):26–45.

    Article  CAS  Google Scholar 

  52. Dekker J, Mirny L. The 3D genome as moderator of chromosomal communication. Cell. 2016;164(6):1110–21. https://doi.org/10.1016/j.cell.2016.02.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Krefting J, Andrade-Navarro MA, Ibn-Salem J. Evolutionary stability of topologically associating domains is associated with conserved gene regulation. BMC Biol. 2018;16(1):87. https://doi.org/10.1186/s12915-018-0556-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Soler-Oliva ME, Guerrero-Martínez JA, Bachetti V, Reyes JC. Analysis of the relationship between coexpression domains and chromatin 3D organization. PLoS Comput Biol. 2017;13(9):e1005708. https://doi.org/10.1371/journal.pcbi.1005708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES, Aiden EL. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014;159(7):1665–80. https://doi.org/10.1016/j.cell.2014.11.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289–93. https://doi.org/10.1126/science.1181369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012;485(7398):376–80. https://doi.org/10.1038/nature11082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ren G, Jin W, Cui K, Rodrigez J, Hu G, Zhang Z, Larson DR, Zhao K. CTCF-mediated enhancer-promoter interaction is a critical regulator of cell-to-cell variation of gene expression. Mol Cell. 2017;67(6):1049–1058.e6. https://doi.org/10.1016/j.molcel.2017.08.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nothjunge S, Nührenberg TG, Grüning BA, Doppler SA, Preissl S, Schwaderer M, Rommel C, Krane M, Hein L, Gilsbach R. DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes. Nat Commun. 2017;8(1):1667. https://doi.org/10.1038/s41467-017-01724-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453(7197):948–51. https://doi.org/10.1038/nature06947.

    Article  CAS  PubMed  Google Scholar 

  61. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ. Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010;467(7314):430–5. https://doi.org/10.1038/nature09380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chereji RV, Bharatula V, Elfving N, Blomberg J, Larsson M, Morozov AV, Broach JR, Björklund S. Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly. Nucleic Acids Res. 2017;45(15):8806–21. https://doi.org/10.1093/nar/gkx491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R, Santos-Simarro F. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell. 2015;161(5):1012–25. https://doi.org/10.1016/j.cell.2015.04.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic Acids Res. 2019;47(D1):D155–62. https://doi.org/10.1093/nar/gky1141.

    Article  PubMed  Google Scholar 

  65. Kim YK, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26(3):775–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP. Vertebrate microRNA genes. Science. 2003;299(5612):1540. https://doi.org/10.1126/science.1080372.

    Article  CAS  PubMed  Google Scholar 

  67. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14(10A):1902–10. https://doi.org/10.1101/gr.2722704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH. An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol. 2019;234(5):5451–65. https://doi.org/10.1002/jcp.27486.

    Article  CAS  PubMed  Google Scholar 

  69. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–34. https://doi.org/10.1038/ncb0309-228.

    Article  CAS  PubMed  Google Scholar 

  70. Ballarino M, Pagano F, Girardi E, Morlando M, Cacchiarelli D, Marchioni M, Proudfoot NJ, Bozzoni I. Coupled RNA processing and transcription of intergenic primary microRNAs. Mol Cell Biol. 2009;29(20):5632–8. https://doi.org/10.1128/MCB.00664-09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chekulaeva M, Filipowicz W. Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol. 2009;21(3):452–60. https://doi.org/10.1016/j.ceb.2009.04.009.

    Article  CAS  PubMed  Google Scholar 

  72. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102–14. https://doi.org/10.1038/nrg2290.

    Article  CAS  PubMed  Google Scholar 

  73. Hibio N, Hino K, Shimizu E, Nagata Y, Ui-Tei K. Stability of miRNA 5′ terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy. Sci Rep. 2012;2:996. https://doi.org/10.1038/srep00996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Calin GA, Croce CM. Investigation of microRNA alterations in leukemias and lymphomas. Methods Enzymol. 2007;427:193–213. https://doi.org/10.1016/S0076-6879(07)27011-9.

    Article  CAS  PubMed  Google Scholar 

  75. Weber B, Stresemann C, Brueckner B, Lyko F. Methylation of human microRNA genes in normal and neoplastic cells. Cell Cycle. 2007;6(9):1001–5. https://doi.org/10.4161/cc.6.9.4209.

    Article  CAS  PubMed  Google Scholar 

  76. Tao BB, Liu XQ, Zhang W, Li S, Dong D, Xiao M, Zhong J. Evidence for the association of chromatin and microRNA regulation in the human genome. Oncotarget. 2017;8(41):70958–66. https://doi.org/10.18632/oncotarget.20214.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setién F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Gitt A, Spiteri I. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007;67(4):1424–9. https://doi.org/10.1158/0008-5472.CAN-06-4218.

    Article  CAS  PubMed  Google Scholar 

  78. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15–20. https://doi.org/10.1016/j.cell.2004.12.035.

    Article  CAS  PubMed  Google Scholar 

  79. Tuddenham L, Wheeler G, Ntounia-Fousara S, Waters J, Hajihosseini MK, Clark I, Dalmay T. The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett. 2006;580(17):4214–7. https://doi.org/10.1016/j.febslet.2006.06.080.

    Article  CAS  PubMed  Google Scholar 

  80. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38(2):228–33. https://doi.org/10.1038/ng1725.

    Article  CAS  PubMed  Google Scholar 

  81. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104(40):15805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ting AH, Suzuki H, Cope L, Schuebel KE, Lee BH, Toyota M, Imai K, Shinomura Y, Tokino T, Baylin SB. A requirement for DICER to maintain full promoter CpG island hypermethylation in human cancer cells. Cancer Res. 2008;68(8):2570–5. https://doi.org/10.1158/0008-5472.CAN-07-6405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Nanda JS, Kumar R, Raghava GP. dbEM: a database of epigenetic modifiers curated from cancerous and normal genomes. Sci Rep. 2016;6:19340. https://doi.org/10.1038/srep19340.

    Article  CAS  Google Scholar 

  84. Copeland RA, Olhava EJ, Scott MP. Targeting epigenetic enzymes for drug discovery. Curr Opin Chem Biol. 2010;14(4):505–10. https://doi.org/10.1016/j.cbpa.2010.06.174.

    Article  CAS  PubMed  Google Scholar 

  85. Jahan-Mihan A, Rodriguez J, Christie C, Sadeghi M, Zerbe T. The role of maternal dietary proteins in development of metabolic syndrome in offspring. Nutrients. 2015;7(11):9185–217. https://doi.org/10.3390/nu7115460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr, International Diabetes Federation Task Force on Epidemiology and Prevention, Hational Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5. https://doi.org/10.1161/CIRCULATIONAHA.109.192644.

    Article  CAS  PubMed  Google Scholar 

  87. Bianco A, Pomara F, Thomas E, Paoli A, Battaglia G, Petrucci M, Proia P, Bellafiore M, Palma A. Type 2 diabetes family histories, body composition and fasting glucose levels: a cross-section analysis in healthy sedentary male and female. Iran J Public Health. 2013;42(7):681–90.

    PubMed  PubMed Central  Google Scholar 

  88. Garg A. Regional adiposity and insulin resistance. J Clin Endocrinol Metab. 2004;89(9):4206–10. https://doi.org/10.1210/jc.2004-0631.

    Article  CAS  PubMed  Google Scholar 

  89. Ndisang JF. Role of heme oxygenase in inflammation, insulin-signalling, diabetes and obesity. Mediat Inflamm. 2010;2010:359732. https://doi.org/10.1155/2010/359732.

    Article  CAS  Google Scholar 

  90. Ginter E, Simko V. Type 2 diabetes mellitus, pandemic in 21st century. In: Diabetes. New York, NY: Springer; 2013. p. 42–50.

    Chapter  Google Scholar 

  91. Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compr Physiol. 2013;3(1):1–58. https://doi.org/10.1002/cphy.c110062.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Karnik S, Kanekar A. Childhood obesity: a global public health crisis. Int J Prev Med. 2012;3(1):1–7.

    PubMed  PubMed Central  Google Scholar 

  93. Maitre L, de Bont J, Casas M, Robinson O, Aasvang GM, Agier L, Andrušaitytė S, Ballester F, Basagaña X, Borràs E, Brochot C, Bustamante M, Carracedo A, de Castro M, Dedele A, Donaire-Gonzalez D, Estivill X, Evandt J, Fossati S, Giorgis-Allemand L, Gonzalez JR, Granum B, Grazuleviciene R, Bjerve Gützkow K, Småstuen Haug L, Hernandez-Ferrer C, Heude B, Ibarluzea J, Julvez J, Karachaliou M, Keun HC, Hjertager Krog N, Lau CE, Leventakou V, Lyon-Caen S, Manzano C, Mason D, McEachan R, Meltzer HM, Petraviciene I, Quentin J, Roumeliotaki T, Sabido E, Saulnier PJ, Siskos AP, Siroux V, Sunyer J, Tamayo I, Urquiza J, Vafeiadi M, van Gent D, Vives-Usano M, Waiblinger D, Warembourg C, Chatzi L, Coen M, van den Hazel P, Nieuwenhuijsen MJ, Slama R, Thomsen C, Wright J, Vrijheid M. Human Early Life Exposome (HELIX) study: a European population-based exposome cohort. BMJ Open. 2018;8(9):e021311. https://doi.org/10.1136/bmjopen-2017-021311.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Al-Hamad D, Raman V. Metabolic syndrome in children and adolescents. Transl Pediatr. 2017;6(4):397–407. https://doi.org/10.21037/tp.2017.10.02.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ, Imperatore G, Williams DE, Bell RA, Wadwa RP, Palla SL, Liu LL, Kershnar A, Daniels SR. Prevalence of cardiovascular disease risk factors in US children and adolescents with diabetes: the SEARCH for diabetes in youth study. Diabetes Care. 2006;29(8):1891–6. https://doi.org/10.2337/dc06-0310.

    Article  PubMed  Google Scholar 

  96. TODAY Study Group. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007;8(2):74–87. https://doi.org/10.1111/j.1399-5448.2007.00237.x.

    Article  Google Scholar 

  97. Weinstock RS, Drews KL, Caprio S, Leibel NI, McKay SV, Zeitler PS, TODAY Study Group. Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: results from the TODAY clinical trial. Obesity (Silver Spring). 2015;23(7):1357–61. https://doi.org/10.1002/oby.21120.

    Article  Google Scholar 

  98. Painter RC, Roseboom TJ, Bleker OP. Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol. 2005;20(3):345–52. https://doi.org/10.1016/j.reprotox.2005.04.005.

    Article  CAS  PubMed  Google Scholar 

  99. Keinan-Boker L, Shasha-Lavsky H, Eilat-Zanani S, Edri-Shur A, Shasha SM. Chronic health conditions in Jewish Holocaust survivors born during World War II. Isr Med Assoc J. 2015;17(4):206–12.

    PubMed  Google Scholar 

  100. Wang Z, Li C, Yang Z, Zou Z, Ma J. Infant exposure to Chinese famine increased the risk of hypertension in adulthood: results from the China Health and Retirement Longitudinal Study. BMC Public Health. 2016;16:435. https://doi.org/10.1186/s12889-016-3122-x.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Wang Z, Li C, Yang Z, Ma J, Zou Z. Fetal and infant exposure to severe Chinese famine increases the risk of adult dyslipidemia: results from the China health and retirement longitudinal study. BMC Public Health. 2017;17(1):488. https://doi.org/10.1186/s12889-017-4421-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Barker DJ. Developmental origins of chronic disease. Public Health. 2012;126(3):185–9. https://doi.org/10.1016/j.puhe.2011.11.014.

    Article  CAS  PubMed  Google Scholar 

  104. Kohan-Ghadr HR, Kadam L, Jain C, Armant DR, Drewlo S. Potential role of epigenetic mechanisms in regulation of trophoblast differentiation, migration, and invasion in the human placenta. Cell Adhes Migr. 2016;10(1-2):126–35. https://doi.org/10.1080/19336918.2015.1098800.

    Article  CAS  Google Scholar 

  105. Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2012;13(2):97–109. https://doi.org/10.1038/nrg3142.

    Article  CAS  PubMed  Google Scholar 

  106. Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23(15):5293–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Michaud EJ, Van Vugt MJ, Bultman SJ, Sweet HO, Davisson MT, Woychik RP. Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev. 1994;8(12):1463–72.

    Article  CAS  PubMed  Google Scholar 

  108. Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23(3):314–8. https://doi.org/10.1038/15490.

    Article  CAS  PubMed  Google Scholar 

  109. Friso S, Udali S, De Santis D, Choi SW. One-carbon metabolism and epigenetics. Mol Asp Med. 2017;54:28–36. https://doi.org/10.1016/j.mam.2016.11.007.

    Article  CAS  Google Scholar 

  110. Yadav DK, Shrestha S, Lillycrop KA, Joglekar CV, Pan H, Holbrook JD, Fall CH, Yajnik CS, Chandak GR. Vitamin B12 supplementation influences methylation of genes associated with type 2 diabetes and its intermediate traits. Epigenomics. 2018;10(1):71–90. https://doi.org/10.2217/epi-2017-0102.

    Article  CAS  PubMed  Google Scholar 

  111. Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J, Thurston A, Huntley JF, Rees WD, Maloney CA, Lea RG. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A. 2007;104(49):19351–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Jin C, Zhuo Y, Wang J, Zhao Y, Xuan Y, Mou D, Liu H, Zhou P, Fang Z, Che L, Xu S. Methyl donors dietary supplementation to gestating sows diet improves the growth rate of offspring and is associating with changes in expression and DNA methylation of insulin-like growth factor-1 gene. J Anim Physiol Anim Nutr. 2018;102(5):1340–50. https://doi.org/10.1111/jpn.12933.

    Article  CAS  Google Scholar 

  113. Aguirre GA, Ita JR, Garza DL, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016;14:3. https://doi.org/10.1186/s12967-015-0762-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sjögren K, Wallenius K, Liu JL, Bohlooly-y M, Pacini G, Svensson L, Törnell J, Isaksson OG, Ahrén B, Jansson JO, Ohlsson C. Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism. Diabetes. 2001;50(7):1539–45.

    Article  PubMed  Google Scholar 

  115. Hussain Z, Khan JA. Food intake regulation by leptin: mechanisms mediating gluconeogenesis and energy expenditure. Asian Pac J Trop Med. 2017;10(10):940–4. https://doi.org/10.1016/j.apjtm.2017.09.003.

    Article  CAS  PubMed  Google Scholar 

  116. García-Cardona MC, Huang F, García-Vivas JM, Lopez-Camarillo C, Del Rio Navarro BE, Olivos EN, Hong-Chong E, Bolaños-Jiménez F, Marchat LA. DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance. Int J Obes. 2014;38(11):1457–65. https://doi.org/10.1038/ijo.2014.30.

    Article  CAS  Google Scholar 

  117. Gali Ramamoorthy T, Allen TJ, Davies A, Harno E, Sefton C, Murgatroyd C, White A. Maternal overnutrition programs epigenetic changes in the regulatory regions of hypothalamic Pomc in the offspring of rats. Int J Obes. 2018;42(8):1431–44. https://doi.org/10.1038/s41366-018-0094-1.

    Article  CAS  Google Scholar 

  118. Millington GW. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab. 2007;4:18. https://doi.org/10.1186/1743-7075-4-18.

    Article  CAS  Google Scholar 

  119. Li X, Tu P, Umar M, Liu Q, Luo W, Yang X, Zhu J, Kong D, Li M. A study on molecular mechanisms of adiposis induced by long-term treatment of high-fat and high-sucrose in C57BL/6J mice. Physiol Res. 2019;68(1):75–87. https://doi.org/10.33549/physiolres.933830.

  120. Masuyama H, Hiramatsu Y. Effects of a high-fat diet exposure in utero on the metabolic syndrome-like phenomenon in mouse offspring through epigenetic changes in adipocytokine gene expression. Endocrinology. 2012;153(6):2823–30. https://doi.org/10.1210/en.2011-2161.

    Article  CAS  PubMed  Google Scholar 

  121. McCurdy CE, Bishop JM, Williams SM, Grayson BE, Smith MS, Friedman JE, Grove KL. Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest. 2009;119(2):323–35. https://doi.org/10.1172/JCI32661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R, Lane RH. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008;41(2):91–102. https://doi.org/10.1677/JME-08-0025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Ding Y, Li J, Liu S, Zhang L, Xiao H, Chen H, Petersen RB, Huang K, Zheng L. DNA hypomethylation of inflammation-associated genes in adipose tissue of female mice after multigenerational high fat diet feeding. Int J Obes. 2014;38(2):198–204. https://doi.org/10.1038/ijo.2013.98.

    Article  CAS  Google Scholar 

  124. Li X, Yan Q, Tang S, Tan Z, Fitzsimmons CJ, Yi K. Effects of maternal feed intake restriction during pregnancy on the expression of growth regulation, imprinting and epigenetic transcription-related genes in foetal goats. Anim Reprod Sci. 2018;198:90–8. https://doi.org/10.1016/j.anireprosci.2018.09.005.

    Article  CAS  PubMed  Google Scholar 

  125. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA. Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr. 2007;97(6):1036–46. https://doi.org/10.1017/S0007114507682920.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005;135(6):1382–6. https://doi.org/10.1093/jn/135.6.1382.

    Article  CAS  PubMed  Google Scholar 

  127. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARα promoter of the offspring. Br J Nutr. 2008;100(2):278–82. https://doi.org/10.1017/S0007114507894438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr. 2007;97(6):1064–73. https://doi.org/10.1017/S000711450769196X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Rajendran P, Ho E, Williams DE, Dashwood RH. Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells. Clin Epigenetics. 2011;3(1):4. https://doi.org/10.1186/1868-7083-3-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc min mice. FASEB J. 2006;20(3):506–8. https://doi.org/10.1096/fj.05-4785fje.

    Article  CAS  PubMed  Google Scholar 

  131. Fernández AF, Fraga MF. The effects of the dietary polyphenol resveratrol on human healthy aging and lifespan. Epigenetics. 2011;6(7):870–4.

    Article  PubMed  Google Scholar 

  132. Singh S, Li SS. Epigenetic effects of environmental chemicals bisphenol a and phthalates. Int J Mol Sci. 2012;13(8):10143–53. https://doi.org/10.3390/ijms130810143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Mandal C, Halder D, Jung KH, Chai YG. Gestational alcohol exposure altered DNA methylation status in the developing fetus. Int J Mol Sci. 2017;18(7):E1386. https://doi.org/10.3390/ijms18071386.

    Article  CAS  PubMed  Google Scholar 

  134. Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res. 2013;35(1):6–16.

    PubMed  PubMed Central  Google Scholar 

  135. Ivorra C, Fraga MF, Bayón GF, Fernández AF, Garcia-Vicent C, Chaves FJ, Redon J, Lurbe E. DNA methylation patterns in newborns exposed to tobacco in utero. J Transl Med. 2015;13:25. https://doi.org/10.1186/s12967-015-0384-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Lee KW, Pausova Z. Cigarette smoking and DNA methylation. Front Genet. 2013;4:132. https://doi.org/10.3389/fgene.2013.00132.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Sundar IK, Nevid MZ, Friedman AE, Rahman I. Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer. J Proteome Res. 2014;13(2):982–96. https://doi.org/10.1021/pr400998n.

    Article  CAS  PubMed  Google Scholar 

  138. Mancebo SE, Wang SQ. Skin cancer: role of ultraviolet radiation in carcinogenesis. Rev Environ Health. 2014;29(3):265–73. https://doi.org/10.1515/reveh-2014-0041.

    Article  CAS  PubMed  Google Scholar 

  139. Ikehata H, Ono T. Significance of CpG methylation for solar UV-induced mutagenesis and carcinogenesis in skin. Photochem Photobiol. 2007;83(1):196–204.

    CAS  PubMed  Google Scholar 

  140. Gesumaria L, Matsui MS, Kluz T, Costa M. Solar-simulated ultraviolet radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinases 1 and 3 in primary human dermal fibroblasts. Exp Dermatol. 2015;24(5):384–5. https://doi.org/10.1111/exd.12675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Vandiver AR, Irizarry RA, Hansen KD, Garza LA, Runarsson A, Li X, Chien AL, Wang TS, Leung SG, Kang S, Feinberg AP. Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin. Genome Biol. 2015;16:80. https://doi.org/10.1186/s13059-015-0644-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Nandakumar V, Vaid M, Tollefsbol TO, Katiyar SK. Aberrant DNA hypermethylation patterns lead to transcriptional silencing of tumor suppressor genes in UVB-exposed skin and UVB-induced skin tumors of mice. Carcinogenesis. 2011;32(4):597–604. https://doi.org/10.1093/carcin/bgq282.

    Article  CAS  PubMed  Google Scholar 

  143. Rehman K, Fatima F, Waheed I, Akash MS. Prevalence of exposure of heavy metals and their impact on health consequences. J Cell Biochem. 2018;119(1):157–84. https://doi.org/10.1002/jcb.26234.

    Article  CAS  PubMed  Google Scholar 

  144. Caffo M, Caruso G, La Fata G, Barresi V, Visalli M, Venza M, Venza I. Heavy metals and epigenetic alterations in brain tumors. Curr Genomics. 2014;15(6):457–63. https://doi.org/10.2174/138920291506150106151847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Young JI, Züchner S, Wang G. Regulation of the epigenome by vitamin C. Annu Rev Nutr. 2015;35:545–64. https://doi.org/10.1146/annurev-nutr-071714-034228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Salemi R, Marconi A, Di Salvatore V, Franco S, Rapisarda V, Libra M. Epigenetic alterations and occupational exposure to benzene, fibers, and heavy metals associated with tumor development. Mol Med Rep. 2017;15(5):3366–71. https://doi.org/10.3892/mmr.2017.6383.

    Article  CAS  PubMed  Google Scholar 

  147. Ryu HW, Lee DH, Won HR, Kim KH, Seong YJ, Kwon SH. Influence of toxicologically relevant metals on human epigenetic regulation. Toxicol Res. 2015;31(1):1–9. https://doi.org/10.5487/TR.2015.31.1.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Zannas AS, Chrousos GP. Epigenetic programming by stress and glucocorticoids along the human lifespan. Mol Psychiatry. 2017;22(5):640–6. https://doi.org/10.1038/mp.2017.35.

    Article  CAS  PubMed  Google Scholar 

  149. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847–54.

    Article  CAS  PubMed  Google Scholar 

  150. Radtke KM, Schauer M, Gunter HM, Ruf-Leuschner M, Sill J, Meyer A, Elbert T. Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment. Transl Psychiatry. 2015;5:e571. https://doi.org/10.1038/tp.2015.63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Zannas AS, Arloth J, Carrillo-Roa T, Iurato S, Röh S, Ressler KJ, Nemeroff CB, Smith AK, Bradley B, Heim C, Menke A. Lifetime stress accelerates epigenetic aging in an urban, African American cohort: relevance of glucocorticoid signaling. Genome Biol. 2015;16:266. https://doi.org/10.1186/s13059-015-0828-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Brainard J, Gobel M, Scott B, Koeppen M, Eckle T. Health implications of disrupted circadian rhythms and the potential for daylight as therapy. Anesthesiology. 2015;122(5):1170–5. https://doi.org/10.1097/ALN.0000000000000596.

    Article  PubMed  Google Scholar 

  153. Qureshi IA, Mehler MF. Epigenetics of sleep and chronobiology. Curr Neurol Neurosci Rep. 2014;14(3):432. https://doi.org/10.1007/s11910-013-0432-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bhatti P, Zhang Y, Song X, Makar KW, Sather CL, Kelsey KT, Houseman EA, Wang P. Nightshift work and genome-wide DNA methylation. Chronobiol Int. 2015;32(1):103–12. https://doi.org/10.3109/07420528.2014.956362.

    Article  CAS  PubMed  Google Scholar 

  155. Adams CD, Jordahl KM, Copeland W, Mirick DK, Song X, Sather CL, Kelsey K, Houseman A, Davis S, Randolph T, Bhatti P. Nightshift work, chronotype, and genome-wide DNA methylation in blood. Epigenetics. 2017;12(10):833–40. https://doi.org/10.1080/15592294.2017.1366407.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA)-Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)-Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain

    Paula Morales-Sánchez, Raúl Fernández Pérez, Pablo Santamarina, Sandra Rodriguez-Rodero, Agustin Fernandez-Fernandez & Mario F. Fraga

  2. Endocrinology, Nutrition, Diabetes and Obesity Unit, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)-Hospital Universitario Central de Asturias (HUCA), Oviedo, Asturias, Spain

    Paula Morales-Sánchez & Sandra Rodriguez-Rodero

  3. Nanomedicine Group, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, Oviedo, Asturias, Spain

    Raúl Fernández Pérez & Mario F. Fraga

Authors
  1. Paula Morales-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raúl Fernández Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pablo Santamarina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandra Rodriguez-Rodero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Agustin Fernandez-Fernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mario F. Fraga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario F. Fraga .

Editor information

Editors and Affiliations

  1. School of Archaeology and Anthropology, Australian National University, Canberra, ACT, Australia

    Justyna J. Miszkiewicz

  2. Department of Medicine-Western Health, University of Melbourne, Melbourne, VIC, Australia

    Sharon L. Brennan-Olsen

  3. Department of Internal Medicine, University of Cantabria, Santander, Cantabria, Spain

    Jose A. Riancho

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Morales-Sánchez, P., Pérez, R.F., Santamarina, P., Rodriguez-Rodero, S., Fernandez-Fernandez, A., Fraga, M.F. (2019). Epigenetics: At the Crossroads Between Genetic and Environmental Determinants of Disease. In: Miszkiewicz, J., Brennan-Olsen, S., Riancho, J. (eds) Bone Health. Springer, Singapore. https://doi.org/10.1007/978-981-13-7256-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-7256-8_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-7255-1

  • Online ISBN: 978-981-13-7256-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation