Skip to main content
SpringerLink
Log in

Future Perspectives in Epigenetic Inheritance

  • Chapter
  • First Online:
Beyond Our Genes

Abstract

Although a growing body of experimental evidence supports the relevance of epigenetic inheritance to mammalian physiology (including humans), the underlying molecular mechanisms are still unknown. The aim of this chapter is to provide a short overview of the best-characterized molecular mechanisms of epigenetic inheritance and then continue and focus on yet to be explored, perspective mechanisms. The chapter concludes with an overview of the potential relevance epigenetic inheritance poses to human health and well-being.

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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. Bateson W, Pellew C. On the genetics of “rogues” among culinary peas (Pisum sativum). J Genet. 1915;5(1):13–36.

    Article  Google Scholar 

  2. Brink RA. A genetic change associated with the R locus in maize which is directed and potentially reversible. Genetics. 1956;41(6):872–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Coe EH. A regular and continuing conversion-type phenomenon at the B locus in maize. Proc Natl Acad Sci U S A. 1959;45(6):828–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hollick JB, Patterson GI, Coe EH Jr, Cone KC, Chandler VL. Allelic interactions heritably alter the activity of a metastable maize pl allele. Genetics. 1995;141(2):709–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pilu R, Panzeri D, Cassani E, Cerino Badone F, Landoni M, Nielsen E. A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait. Heredity (Edinb). 2009;102(3):236–45.

    Article  CAS  Google Scholar 

  6. Sidorenko LV, Peterson T. Transgene-induced silencing identifies sequences involved in the establishment of paramutation of the maize p1 gene. Plant Cell. 2001;13(2):319–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Walker EL, Robbins TP, Bureau TE, Kermicle J, Dellaporta SL. Transposon-mediated chromosomal rearrangements and gene duplications in the formation of the maize R-r complex. EMBO J. 1995;14(10):2350–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Panavas T, Weir J, Walker EL. The structure and paramutagenicity of the R-marbled haplotype of Zea mays. Genetics. 1999;153(2):979–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Herman H, Lu M, Anggraini M, Sikora A, Chang Y, Yoon BJ, et al. Trans allele methylation and paramutation-like effects in mice. Nat Genet. 2003;34(2):199–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. The Pea (Pisum sativum L.). Rogue paramutation is accompanied by alterations in the methylation pattern of specific genomic sequences. Epigenomes. 2017;1(1):6.

    Google Scholar 

  11. Duhl DM, Vrieling H, Miller KA, Wolff GL, Barsh GS. Neomorphic agouti mutations in obese yellow mice. Nat Genet. 1994;8(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  12. Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23(3):314–8.

    Article  CAS  PubMed  Google Scholar 

  13. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL 3rd, et al. The mouse fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell. 1997;90(1):181–92.

    Article  CAS  PubMed  Google Scholar 

  14. Reed SC. The inheritance and expression of fused, a new mutation in the house mouse. Genetics. 1937;22(1):1–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Rakyan VK, Chong S, Champ ME, Cuthbert PC, Morgan HD, Luu KV, et al. Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A. 2003;100(5):2538–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Derkatch IL, Chernoff YO, Kushnirov VV, Inge-Vechtomov SG, Liebman SW. Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics. 1996;144(4):1375–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hackett JA, Zylicz JJ, Surani MA. Parallel mechanisms of epigenetic reprogramming in the germline. Trends Genet. 2012;28(4):164–74.

    Article  CAS  PubMed  Google Scholar 

  18. Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, et al. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell. 2012;48(6):849–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature. 2006;441(7092):469–74.

    Article  CAS  PubMed  Google Scholar 

  20. Wagner KD, Wagner N, Ghanbarian H, Grandjean V, Gounon P, Cuzin F, et al. RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. Dev Cell. 2008;14(6):962–9.

    Article  CAS  PubMed  Google Scholar 

  21. Grandjean V, Gounon P, Wagner N, Martin L, Wagner KD, Bernex F, et al. The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development. 2009;136(21):3647–55.

    Article  CAS  PubMed  Google Scholar 

  22. Rechavi O, Minevich G, Hobert O. Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell. 2011;147(6):1248–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stein P, Svoboda P, Anger M, Schultz RM. RNAi: mammalian oocytes do it without RNA-dependent RNA polymerase. RNA. 2003;9(2):187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Malone CD, Hannon GJ. Small RNAs as guardians of the genome. Cell. 2009;136(4):656–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Toth KF, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008;31(6):785–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev. 2008;22(7):908–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, et al. Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature. 2011;480(7376):264–7.

    Article  CAS  PubMed  Google Scholar 

  28. Rouget C, Papin C, Boureux A, Meunier AC, Franco B, Robine N, et al. Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature. 2010;467(7319):1128–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Luteijn MJ, Ketting RF. PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nat Rev Genet. 2013;14(8):523–34.

    Article  CAS  PubMed  Google Scholar 

  30. Popp C, Dean W, Feng S, Cokus SJ, Andrews S, Pellegrini M, et al. Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature. 2010;463(7284):1101–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sasaki H, Matsui Y. Epigenetic events in mammalian germ-cell development: reprogramming and beyond. Nat Rev Genet. 2008;9(2):129–40.

    Article  CAS  PubMed  Google Scholar 

  32. Balhorn R. The protamine family of sperm nuclear proteins. Genome Biol. 2007;8(9):227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460(7254):473–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kimmins S, Sassone-Corsi P. Chromatin remodelling and epigenetic features of germ cells. Nature. 2005;434(7033):583–9.

    Article  CAS  PubMed  Google Scholar 

  35. De La Fuente R, Viveiros MM, Wigglesworth K, Eppig JJ. ATRX, a member of the SNF2 family of helicase/ATPases, is required for chromosome alignment and meiotic spindle organization in metaphase II stage mouse oocytes. Dev Biol. 2004;272(1):1–14.

    Article  CAS  Google Scholar 

  36. Teranishi T, Tanaka M, Kimoto S, Ono Y, Miyakoshi K, Kono T, et al. Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1foo in nuclear transfer. Dev Biol. 2004;266(1):76–86.

    Article  CAS  PubMed  Google Scholar 

  37. Irvine DV, Zaratiegui M, Tolia NH, Goto DB, Chitwood DH, Vaughn MW, et al. Argonaute slicing is required for heterochromatic silencing and spreading. Science. 2006;313(5790):1134–7.

    Article  CAS  PubMed  Google Scholar 

  38. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science. 2002;297(5588):1833–7.

    Article  CAS  PubMed  Google Scholar 

  39. Buker SM, Iida T, Buhler M, Villen J, Gygi SP, Nakayama J, et al. Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast. Nat Struct Mol Biol. 2007;14(3):200–7.

    Article  CAS  PubMed  Google Scholar 

  40. Wassenegger M, Heimes S, Riedel L, Sanger HL. RNA-directed de novo methylation of genomic sequences in plants. Cell. 1994;76(3):567–76.

    Article  CAS  PubMed  Google Scholar 

  41. Mette MF, Aufsatz W, van der Winden J, Matzke MA, Matzke AJ. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J. 2000;19(19):5194–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gu SG, Pak J, Guang S, Maniar JM, Kennedy S, Fire A. Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint. Nat Genet. 2012;44(2):157–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Burton NO, Burkhart KB, Kennedy S. Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2011;108(49):19683–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, et al. Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science. 2011;332(6031):848–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn MP, Cording AC, et al. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell. 2012;150(1):88–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhai J, Liu J, Liu B, Li P, Meyers BC, Chen X, et al. Small RNA-directed epigenetic natural variation in Arabidopsis thaliana. PLoS Genet. 2008;4(4):e1000056.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Katz DJ, Edwards TM, Reinke V, Kelly WG. A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory. Cell. 2009;137(2):308–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Klosin A, Casas E, Hidalgo-Carcedo C, Vavouri T, Lehner B. Transgenerational transmission of environmental information in C. elegans. Science. 2017;356(6335):320–3.

    Article  CAS  PubMed  Google Scholar 

  49. Camacho J, Truong L, Kurt Z, Chen YW, Morselli M, Gutierrez G, et al. The memory of environmental chemical exposure in C. elegans is dependent on the Jumonji demethylases jmjd-2 and jmjd-3/utx-1. Cell Rep. 2018;23(8):2392–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Siklenka K, Erkek S, Godmann M, Lambrot R, McGraw S, Lafleur C, et al. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science. 2015;350(6261):aab2006.

    Article  PubMed  CAS  Google Scholar 

  51. Javurek AB, Spollen WG, Ali AM, Johnson SA, Lubahn DB, Bivens NJ, et al. Discovery of a novel seminal fluid microbiome and influence of estrogen receptor alpha genetic status. Sci Rep. 2016;6:23027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–14.

    Article  CAS  Google Scholar 

  53. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4578–85.

    Article  CAS  PubMed  Google Scholar 

  55. Chung H, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell. 2012;149(7):1578–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011;108(7):3047–52.

    Article  PubMed  Google Scholar 

  57. Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141(2):599–609.. e1-3

    Article  CAS  PubMed  Google Scholar 

  59. Stern S, Fridmann-Sirkis Y, Braun E, Soen Y. Epigenetically heritable alteration of fly development in response to toxic challenge. Cell Rep. 2012;1(5):528–42.

    Article  CAS  PubMed  Google Scholar 

  60. Fridmann-Sirkis Y, Stern S, Elgart M, Galili M, Zeisel A, Shental N, et al. Delayed development induced by toxicity to the host can be inherited by a bacterial-dependent, transgenerational effect. Front Genet. 2014;5:27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008;134(2):577–94.

    Article  CAS  PubMed  Google Scholar 

  62. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science. 2010;328(5975):228–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010;5(2):e9085.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214.

    Article  PubMed  CAS  Google Scholar 

  65. Leclercq S, Mian FM, Stanisz AM, Bindels LB, Cambier E, Ben-Amram H, et al. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nat Commun. 2017;8:15062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Neuman H, Forsythe P, Uzan A, Avni O, Koren O. Antibiotics in early life: dysbiosis and the damage done. FEMS Microbiol Rev. 2018;42(4):489–99.

    CAS  PubMed  Google Scholar 

  67. Werren JH, Baldo L, Clark ME. Wolbachia: master manipulators of invertebrate biology. Nat Rev Microbiol. 2008;6(10):741–51.

    Article  CAS  PubMed  Google Scholar 

  68. Elgart M, Stern S, Salton O, Gnainsky Y, Heifetz Y, Soen Y. Impact of gut microbiota on the fly’s germ line. Nat Commun. 2016;7:11280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Devanapally S, Ravikumar S, Jose AM. Double-stranded RNA Made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. Proc Natl Acad Sci U S A. 2015;112(7):2133–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing XY, et al. Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science. 2016;351(6271):391–6.

    Article  CAS  PubMed  Google Scholar 

  71. El-Mogy M, Lam B, Haj-Ahmad TA, McGowan S, Yu D, Nosal L, et al. Diversity and signature of small RNA in different bodily fluids using next generation sequencing. BMC Genomics. 2018;19(1):408.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Carell T, Kurz MQ, Muller M, Rossa M, Spada F. Non-canonical bases in the genome: the regulatory information layer in DNA. Angew Chem Int Ed Engl. 2018;57(16):4296–312.

    Article  CAS  PubMed  Google Scholar 

  74. Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet. 2017;18(9):517–34.

    Article  CAS  PubMed  Google Scholar 

  75. Wang L, Zhou Y, Xu L, Xiao R, Lu X, Chen L, et al. Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex. Nature. 2015;523(7562):621–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Raiber EA, Murat P, Chirgadze DY, Beraldi D, Luisi BF, Balasubramanian S. 5-Formylcytosine alters the structure of the DNA double helix. Nat Struct Mol Biol. 2015;22(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  77. Koziol MJ, Bradshaw CR, Allen GE, Costa ASH, Frezza C, Gurdon JB. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol. 2016;23(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  78. Lu M, Campbell JL, Boye E, Kleckner N. SeqA: a negative modulator of replication initiation in E. coli. Cell. 1994;77(3):413–26.

    Article  CAS  PubMed  Google Scholar 

  79. Laengle-Rouault F, Maenhaut-Michel G, Radman M. GATC sequence and mismatch repair in Escherichia coli. EMBO J. 1986;5(8):2009–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Roberts D, Hoopes BC, McClure WR, Kleckner N. IS10 transposition IS regulated by DNA adenine methylation. Cell. 1985;43(1):117–30.

    Article  CAS  PubMed  Google Scholar 

  81. Yao B, Cheng Y, Wang Z, Li Y, Chen L, Huang L, et al. DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress. Nat Commun. 2017;8(1):1122.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Boccaletto P, Machnicka MA, Purta E, Piatkowski P, Baginski B, Wirecki TK, et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2018;46(D1):D303–D7.

    Article  CAS  PubMed  Google Scholar 

  83. Kiani J, Grandjean V, Liebers R, Tuorto F, Ghanbarian H, Lyko F, et al. RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLoS Genet. 2013;9(5):e1003498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, Kellner S, et al. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012;19(9):900–5.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang Y, Zhang X, Shi J, Tuorto F, Li X, Liu Y, et al. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nat Cell Biol. 2018;20(5):535–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Collinge J. Mammalian prions and their wider relevance in neurodegenerative diseases. Nature. 2016;539(7628):217–26.

    Article  PubMed  Google Scholar 

  87. Prusiner SB, Scott MR, DeArmond SJ, Cohen FE. Prion protein biology. Cell. 1998;93(3):337–48.

    Article  CAS  PubMed  Google Scholar 

  88. Lacroute F. Non-Mendelian mutation allowing ureidosuccinic acid uptake in yeast. J Bacteriol. 1971;106(2):519–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wickner RB. [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. Science. 1994;264(5158):566–9.

    Article  CAS  PubMed  Google Scholar 

  90. Derkatch IL, Bradley ME, Hong JY, Liebman SW. Prions affect the appearance of other prions: the story of [PIN(+)]. Cell. 2001;106(2):171–82.

    Article  CAS  PubMed  Google Scholar 

  91. Sondheimer N, Lindquist S. Rnq1: an epigenetic modifier of protein function in yeast. Mol Cell. 2000;5(1):163–72.

    Article  CAS  PubMed  Google Scholar 

  92. Ghaemmaghami S. Biology and Genetics of PrP Prion Strains. Cold Spring Harb Perspect Med. 2017;7(8).

    Article  CAS  Google Scholar 

  93. Chakrabortee S, Byers JS, Jones S, Garcia DM, Bhullar B, Chang A, et al. Intrinsically disordered proteins drive emergence and inheritance of biological traits. Cell. 2016;167(2):369–81.. e12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Beisson J, Sonneborn TM. Cytoplasmic inheritance of the Organization of the Cell Cortex in Paramecium Aurelia. Proc Natl Acad Sci U S A. 1965;53:275–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hirt RP, Horner DS. Organelles, genomes, and eukaryote phylogeny: an evolutionary synthesis in the age of genomics. Boca Raton: CRC Press; 2004. 388 p. p.

    Google Scholar 

  96. Cheng MY, Hartl FU, Horwich AL. The mitochondrial chaperonin hsp60 is required for its own assembly. Nature. 1990;348(6300):455–8.

    Article  CAS  PubMed  Google Scholar 

  97. Rasmann S, De Vos M, Casteel CL, Tian D, Halitschke R, Sun JY, et al. Herbivory in the previous generation primes plants for enhanced insect resistance. Plant Physiol. 2012;158(2):854–63.

    Article  CAS  PubMed  Google Scholar 

  98. Agrawal AA, Laforsch C, Tollrian R. Transgenerational induction of defences in animals and plants. Nature. 1999;401:60–3.

    Article  CAS  Google Scholar 

  99. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727):1466–9.

    Article  CAS  PubMed  Google Scholar 

  100. Bhandari RK, vom Saal FS, Tillitt DE. Transgenerational effects from early developmental exposures to bisphenol A or 17alpha-ethinylestradiol in medaka, Oryzias latipes. Sci Rep. 2015;5:9303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One. 2012;7(2):e31901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Dolinoy DC, Huang D, Jirtle RL. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A. 2007;104(32):13056–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Waterland RA, Dolinoy DC, Lin JR, Smith CA, Shi X, Tahiliani KG. Maternal methyl supplements increase offspring DNA methylation at Axin fused. Genesis. 2006;44(9):401–6.

    Article  CAS  PubMed  Google Scholar 

  104. 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 

  105. 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.

    Article  CAS  PubMed  Google Scholar 

  106. Leese HJ, Hugentobler SA, Gray SM, Morris DG, Sturmey RG, Whitear SL, et al. Female reproductive tract fluids: composition, mechanism of formation and potential role in the developmental origins of health and disease. Reprod Fertil Dev. 2008;20(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  107. Hochberg Z, Feil R, Constancia M, Fraga M, Junien C, Carel JC, et al. Child health, developmental plasticity, and epigenetic programming. Endocr Rev. 2011;32(2):159–224.

    Article  CAS  PubMed  Google Scholar 

  108. Jodar M, Sendler E, Krawetz SA. The protein and transcript profiles of human semen. Cell Tissue Res. 2016;363(1):85–96.

    Article  CAS  PubMed  Google Scholar 

  109. Poiani A. Complexity of seminal fluid: a review. Behav Ecol Sociobiol. 2006;60(3):289–310.

    Article  Google Scholar 

  110. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA. Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol. 2012;188(5):2445–54.

    Article  CAS  PubMed  Google Scholar 

  111. Tremellen KP, Seamark RF, Robertson SA. Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus. Biol Reprod. 1998;58(5):1217–25.

    Article  CAS  PubMed  Google Scholar 

  112. Robertson SA. Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res. 2005;322(1):43–52.

    Article  PubMed  Google Scholar 

  113. Bromfield JJ, Schjenken JE, Chin PY, Care AS, Jasper MJ, Robertson SA. Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc Natl Acad Sci U S A. 2014;111(6):2200–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sharkey DJ, Tremellen KP, Briggs NE, Dekker GA, Robertson SA. Seminal plasma transforming growth factor-beta, activin a and follistatin fluctuate within men over time. Hum Reprod. 2016;31(10):2183–91.

    Article  CAS  PubMed  Google Scholar 

  115. Sharkey DJ, Tremellen KP, Briggs NE, Dekker GA, Robertson SA. Seminal plasma pro-inflammatory cytokines interferon-gamma (IFNG) and C-X-C motif chemokine ligand 8 (CXCL8) fluctuate over time within men. Hum Reprod. 2017;32(7):1373–81.

    Article  CAS  PubMed  Google Scholar 

  116. Binder NK, Sheedy JR, Hannan NJ, Gardner DK. Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model. Mol Hum Reprod. 2015;21(5):424–34.

    Article  CAS  PubMed  Google Scholar 

  117. Javurek AB, Spollen WG, Johnson SA, Bivens NJ, Bromert KH, Givan SA, et al. Consumption of a high-fat diet alters the seminal fluid and gut microbiomes in male mice. Reprod Fertil Dev. 2017;29(8):1602–12.

    Article  CAS  PubMed  Google Scholar 

  118. Prüss-Üstün A, Wolf J, Corvalán C, Bos R, Neira M, World Health Organization, et al. Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. 2nd ed. Geneva, Switzerland: World Health Organization; 2016. xxiii. p. 147.

    Google Scholar 

  119. Bygren LO, Kaati G, Edvinsson S. Longevity determined by paternal ancestors’ nutrition during their slow growth period. Acta Biotheor. 2001;49(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  120. Kaati G, Bygren LO, Edvinsson S. Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet. 2002;10(11):682–8.

    Article  CAS  PubMed  Google Scholar 

  121. Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M, et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 2006;14(2):159–66.

    Article  PubMed  Google Scholar 

  122. Wang Y, Beydoun MA. The obesity epidemic in the United States--gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev. 2007;29:6–28.

    Article  CAS  PubMed  Google Scholar 

  123. Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006;1(1):11–25.

    Article  PubMed  Google Scholar 

  124. Grun F, Blumberg B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006;147(6 Suppl):S50–5.

    Article  CAS  PubMed  Google Scholar 

  125. Janesick AS, Shioda T, Blumberg B. Transgenerational inheritance of prenatal obesogen exposure. Mol Cell Endocrinol. 2014;398(1–2):31–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003;72(1):156–60.

    Article  CAS  PubMed  Google Scholar 

  127. Cortessis VK, Azadian M, Buxbaum J, Sanogo F, Song AY, Sriprasert I, et al. Comprehensive meta-analysis reveals association between multiple imprinting disorders and conception by assisted reproductive technology. J Assist Reprod Genet. 2018;35(6):943–52.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Rexhaj E, Paoloni-Giacobino A, Rimoldi SF, Fuster DG, Anderegg M, Somm E, et al. Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span. J Clin Invest. 2013;123(12):5052–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Chen M, Wu L, Zhao J, Wu F, Davies MJ, Wittert GA, et al. Altered glucose metabolism in mouse and humans conceived by IVF. Diabetes. 2014;63(10):3189–98.

    Article  CAS  PubMed  Google Scholar 

  130. Feuer SK, Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, et al. Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis. Endocrinology. 2014;155(5):1956–69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Lane M, Robker RL, Robertson SA. Parenting from before conception. Science. 2014;345(6198):756–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Helmholtz Zentum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Neuherberg, Germany

    Jonatan Darr

  2. German Center for Diabetes Research (DZD), Neuherberg, Germany

    Jonatan Darr

Authors
  1. Jonatan Darr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonatan Darr .

Editor information

Editors and Affiliations

  1. Head of the Environmental Epigenetics Group, Institute of Experimental Genetics & German Center for Diabetes Research (DZD), Helmholtz Zentrum München GmbH – German Research Center for Environmental Health, Neuherberg, Bayern, Germany

    Raffaele Teperino

Glossary

Glossary

The Central dogma was proposed by Francis Crick in the 50’s and stated that information generally flows from DNA to proteins via intermittent RNA molecules but cannot flow back from proteins to DNA.

Cretzfeldt-Jakob disease (CJD) is a fatal brain disease caused by a prion particle of the PrP protein encouded by the PRNP gene. Can appear as familial, sporadic or acquired disease.

Digital health aims at improving healthcare and allow for a more personalized care through the use of information and communication technologies.

Dysbiosis is a shift in the relative abundances of different microbial taxa comprising the microbiota of a sick organisms compared to taxa observed in healthy organisms.

Endocrine disrupting chemicals are synthetic chemicals that can interfere with the endocrine signaling system. Can cause infertility and lead to the development of cancer, metabolic disorders, birth defects and developmental disorders.

Environmental health is defined as a branch of public health that addresses the direct pathological impacts of chemicals, radiation and some biological agents, and the effects on health and wellbeing of the broad physical, psychological, social and aesthetic environment, which includes housing, urban development, land use and transport.

Environmental protection aims to conserve natural resources, biodiversity and the ecosystem through the implementation of various policies and procedures that protect the environment for the benefit of humans and the ecosystem.

Epialleles are genetically identical but variably expressed alleles. This variable expression is due to epigenetic modifications that are established during early development.

Epigenetic inheritance is defined as mitotically and/or meiotically heritable changes in gene expression that do not result from changes in the DNA sequence. Several different phenomena observed across different kingdoms can be described as epigenetic inheritance.

Gemmules are hypothetical particles suggested by Charles Darwin as part of his Pangenesis theory. These particles are emitted from every tissue and migrate to germ cells where they mediate inheritance. These particles were suggested to contribute to the development of the embryo and for phenotypic traits of progeny. In effect Darwin suggested that acquired somatic traits can be carried on to the offspring via the gemmules.

Germ-free mice are mice grown in sterile conditions which allow to maintain the mice void of any microbiota.

Gnotobiotic mice are mice with a defined set of bacteria and microorganisms.

The Hypothalamic-pituitary-adrenal axis is a major neuroendocrine system that controls stress reactions and regulates multiple processes including digestion, energy storage and expenditure, immunity, mood, sexuality and more. Comprised from the intricate interactions between the hypothalamus, the pituitary gland, the adrenal glands and their respective endocrine signaling factors.

In-vitro fertilization is the process of oocyte fertilization with sperm outside the body and in cell culture.

Imprinting disorders are a collection of congenital disorders that stem from miss-regulation of imprinted loci, which are normally expressed from only one parental allele (maternal or paternal). This miss-regulation can stem from deletions, sense mutations and hyper/hypo-methylation.

Jasmonates are lipid based plant hormones that regulate a wide range of processes including growth, photosynthesis and reproductive development.

Kairomones are signaling molecules that mediate interspecies interactions in a way that benefits the recipient of the signal rather than the secreting party.

Kuru is another fatal neurodegenerative disorder that was common among the Fore people of New- Guinea. As with CJD, a prion strain of the PrP protein caused the disease which was transmitted within the tribe through ritualistic cannibalism.

The Maternal to zygotic transition is an early stage of embryonic development during which the zygotic genome because transcriptionally active and maternaly deposited transcripts are degraded.

The Microbiota is the collection of bacteria, fungi and viruses that live as commensal, symbiotic or pathogenic microorganisms of multicellular organisms.

Obesogens are chemicals that disrupt normal development and homeostatic controls of adipogenesis, lipid metabolism and energy balance in such a way that can induce obesity.

Pangenesis is Charles Darwin’s theory of inheritance published in his book ‘The Variation of Animals and Plants under Domestication’ published at 1868. Pangenesis complemented Darwin’s theory of natural selection in that in proposed a mechanisms for inheritance and development namely Gemmules.

Paramutation involves trans-communication between homologous sequences. This communication establishes heritable changes in chromatin structure that often correlate with alterations in DNA methylation. Loci implicated in paramutation can have three types of allele: alleles that do not participate in paramutation are termed neutral or non-paramutagenic; sensitive alleles are termed paramutable; and alleles that induce the change are paramutagenic.

Pharmacovigilance is the study field related to detection, assessment and prevention of adverse effects caused about by pharmaceutical products with the overall aim of minimizing these risks.

Phytohormones are plant hormones that can control multiple aspects of development starting with reproduction and embryogenesis, through pathogen defense and stress tolerance and more. Phytohormones can be secreted from all cells of the plant and act locally or distally.

Prions are misfolded proteins that have the surprising capacity to self-propagate in an infectious manner. An interaction between a native protein with the misfolded prion protein induces misfolding of the former into a prion particle that can propagate itself further.

Specific pathogen free mice are mice grown free of specific pathogenic infections and certified to be kept under these conditions.

Teratogenic compounds are compounds that cause developmental malformations, a well-known example is thalidomide.

Weismann barrier is a central concept proposed by August Weismann which maintains that germ cell are strictly separated from somatic cells and can only arise from an immortal germ cell lineage. This concept requires genetic information to flow in a unidirectional manner from germ cells to soma, basically excluding any type of soma to germ line information transfer.

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Darr, J. (2020). Future Perspectives in Epigenetic Inheritance. In: Teperino, R. (eds) Beyond Our Genes. Springer, Cham. https://doi.org/10.1007/978-3-030-35213-4_12

Download citation

Publish with us

Policies and ethics

Search

Navigation