Skip to main content
SpringerLink
Log in

The (not so) Controversial Role of DNA Methylation in Epigenetic Inheritance Across Generations

  • Chapter
  • First Online:
Beyond Our Genes

Abstract

It has been demonstrated originally in plants that phenotypic traits, such as floral symmetry, can be caused by changes of methylation patterns of specific genes. Such traits can be transgenerationally inherited for multiple generations and remain associated with cytosine methylation patterns. Whether genomic methylation may also contribute to epigenetic inheritance across generations in vertebrates and notably in mammals is still more controversial. One reason for this tentativeness is the dual occurrence of global genomic de-methylation first in pre-implantation embryos and subsequently in primordial germ cells (PGCs) of mammals. Although gene focused cases of epigenetic inheritance associated with genomic DNA methylation have been well studied mostly in rodents (such as imprinted genes and the Agouti viable yellow, Avy, allele), it is still a matter of debate whether genomic DNA methylation may provide a more general mechanism for the epigenetic inheritance of acquired traits across generations. We review the current literature on this topic with a focus on the potential role of DNA methylation for epigenetic inheritance across generations in mammals.

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. Hotchkiss RD. The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J Biol Chem. 1948;175(1):315-332. Epub 1948/08/01. PubMed PMID: 18873306.

    Google Scholar 

  2. Bird AP. CpG-rich islands and the function of DNA methylation. Nature .1986;321(6067):209-213. Epub 1986/05/15. doi: https://doi.org/10.1038/321209a0. PubMed PMID: 2423876.

    Article  CAS  PubMed  Google Scholar 

  3. Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene. 2002;21(35):5427-5440. Epub 2002/08/03. doi: https://doi.org/10.1038/sj.onc.1205600. PubMed PMID: 12154405.

    Article  CAS  PubMed  Google Scholar 

  4. Feng W, Zhou L, Wang H, Hu Z, Wang X, Fu J, et al. Functional analysis of DNA methylation of the PACSIN1 promoter in pig peripheral blood mononuclear cells. J Cell Biochem. 2019;120(6):10118-10127. Epub 2018/12/12. doi: https://doi.org/10.1002/jcb.28295. PubMed PMID: 30537176.

    Article  PubMed  CAS  Google Scholar 

  5. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484-492. Epub 2012/05/30. doi: https://doi.org/10.1038/nrg3230. PubMed PMID: 22641018.

    Article  CAS  PubMed  Google Scholar 

  6. Pai AA, Bell JT, Marioni JC, Pritchard JK, Gilad Y. A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues. PLoS Genet. 2011;7(2):e1001316. Epub 2011/03/09. doi: https://doi.org/10.1371/journal.pgen.1001316. PubMed PMID: 21383968; PubMed Central PMCID: PMCPMC3044686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhou J, Sears RL, Xing X, Zhang B, Li D, Rockweiler NB, et al. Tissue-specific DNA methylation is conserved across human, mouse, and rat, and driven by primary sequence conservation. BMC Genomics. 2017;18(1):724. Epub 2017/09/14. doi: https://doi.org/10.1186/s12864-017-4115-6. PubMed PMID: 28899353; PubMed Central PMCID: PMCPMC5596466.

  8. Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem. 2005;74:481-514. Epub 2005/06/15. doi: https://doi.org/10.1146/annurev.biochem.74.010904.153721. PubMed PMID: 15952895.

    Article  CAS  PubMed  Google Scholar 

  9. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992;69(6):915-926. Epub 1992/06/12. PubMed PMID: 1606615.

    Article  CAS  PubMed  Google Scholar 

  10. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science. 2001;293(5532):1068-1070. Epub 2001/08/11. doi: https://doi.org/10.1126/science.1063852. PubMed PMID: 11498573.

    Article  CAS  PubMed  Google Scholar 

  11. Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nat Rev Genet. 2013;14(3):204-220. Epub 2013/02/13. doi: https://doi.org/10.1038/nrg3354. PubMed PMID: 23400093.

    Article  CAS  PubMed  Google Scholar 

  12. Hsieh CL, Lieber MR. CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J. 1992;11(1):315-325. Epub 1992/01/01. PubMed PMID: 1371250; PubMed Central PMCID: PMCPMC556452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6(8):597-610. Epub 2005/09/02. doi: https://doi.org/10.1038/nrg1655. PubMed PMID: 16136652.

    Article  CAS  PubMed  Google Scholar 

  14. Yang X, Lay F, Han H, Jones PA. Targeting DNA methylation for epigenetic therapy. Trends Pharmacol Sci. 2010;31(11):536-546. Epub 2010/09/18. doi: https://doi.org/10.1016/j.tips.2010.08.001. PubMed PMID: 20846732; PubMed Central PMCID: PMCPMC2967479.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Wu TP, Wang T, Seetin MG, Lai Y, Zhu S, Lin K, et al. DNA methylation on N(6)-adenine in mammalian embryonic stem cells. Nature. 2016;532(7599):329-333. Epub 2016/03/31. doi: https://doi.org/10.1038/nature17640. PubMed PMID: 27027282; PubMed Central PMCID: PMCPMC4977844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xiao CL, Zhu S, He M, Chen, Zhang Q, Chen Y, et al. N(6)-Methyladenine DNA Modification in the Human Genome. Mol Cell. 2018;71(2):306-318 e7. Epub 2018/07/19. doi: https://doi.org/10.1016/j.molcel.2018.06.015. PubMed PMID: 30017583.

    Article  PubMed  CAS  Google Scholar 

  17. Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizabal-Corrales D, et al. DNA Methylation on N6-Adenine in C. elegans. Cell. 2015;161(4):868-878. Epub 2015/05/06. doi: https://doi.org/10.1016/j.cell.2015.04.005. PubMed PMID: 25936839; PubMed Central PMCID: PMCPMC4427530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ma C, Niu R, Huang T, Shao LW, Peng Y, Ding W, et al. N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation. Nat Cell Biol. 2019;21(3):319-327. Epub 2018/12/05. doi: https://doi.org/10.1038/s41556-018-0238-5. PubMed PMID: 30510156.

    Article  PubMed  CAS  Google Scholar 

  19. Miska EA, Ferguson-Smith AC. Transgenerational inheritance: Models and mechanisms of non-DNA sequence-based inheritance. Science. 2016;354(6308):59-63. Epub 2016/11/16. doi: https://doi.org/10.1126/science.aaf4945. PubMed PMID: 27846492.

    Article  CAS  PubMed  Google Scholar 

  20. Jaenisch R. DNA methylation and imprinting: why bother? Trends Genet. 1997;13(8):323-329. Epub 1997/08/01. PubMed PMID: 9260519.

    Article  CAS  PubMed  Google Scholar 

  21. Brink RA. A Genetic Change Associated with the R Locus in Maize Which Is Directed and Potentially Reversible. Genetics. 1956;41(6):872-889. Epub 1956/11/01. PubMed PMID: 17247669; PubMed Central PMCID: PMCPMC1224369.

    Google Scholar 

  22. Arteaga-Vazquez MA, Chandler VL. Paramutation in maize: RNA mediated trans-generational gene silencing. Curr Opin Genet Dev. 2010;20(2):156-163. Epub 2010/02/16. doi: https://doi.org/10.1016/j.gde.2010.01.008. PubMed PMID: 20153628; PubMed Central PMCID: PMCPMC2859986.

    Article  CAS  Google Scholar 

  23. Cubas P, Vincent C, Coen E. An epigenetic mutation responsible for natural variation in floral symmetry. Nature. 1999;401(6749):157-161. Epub 1999/09/18. doi: https://doi.org/10.1038/43657. PubMed PMID: 10490023.

    Article  CAS  PubMed  Google Scholar 

  24. Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol. 2009;84(2):131-176. Epub 2009/07/18. PubMed PMID: 19606595.

    Article  PubMed  Google Scholar 

  25. Uller T, English S, Pen I. When is incomplete epigenetic resetting in germ cells favoured by natural selection? Proc Biol Sci. 2015;282(1811). Epub 2015/07/03. doi: https://doi.org/10.1098/rspb.2015.0682. PubMed PMID: 26136447; PubMed Central PMCID: PMCPMC4528548.

    Article  PubMed Central  Google Scholar 

  26. Houri-Zeevi L, Rechavi O. A Matter of Time: Small RNAs Regulate the Duration of Epigenetic Inheritance. Trends Genet. 2017;33(1):46-57. Epub 2016/12/13. doi: https://doi.org/10.1016/j.tig.2016.11.001. PubMed PMID: 27939252.

    Article  CAS  PubMed  Google Scholar 

  27. 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. Epub 2003/05/13. doi: https://doi.org/10.1038/ng1162. PubMed PMID: 12740578; PubMed Central PMCID: PMCPMC2744043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rassoulzadegan M, Magliano M, Cuzin F. Transvection effects involving DNA methylation during meiosis in the mouse. EMBO J. 2002;21(3):440-450. Epub 2002/02/02. doi: https://doi.org/10.1093/emboj/21.3.440. PubMed PMID: 11823436; PubMed Central PMCID: PMCPMC125843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cambareri EB, Jensen BC, Schabtach E, Selker EU. Repeat-induced G-C to A-T mutations in Neurospora. Science. 1989;244(4912):1571-1575. Epub 1989/06/30. doi: https://doi.org/10.1126/science.2544994. PubMed PMID: 2544994.

    Article  CAS  PubMed  Google Scholar 

  30. Feng S, Jacobsen SE, Reik W. Epigenetic reprogramming in plant and animal development. Science. 2010;330(6004):622-7. Epub 2010/10/30. doi: 10.1126/science.1190614. PubMed PMID: 21030646; PubMed Central PMCID: PMCPMC2989926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Law JA, Jacobsen SE. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet. 2010;11(3):204-20. Epub 2010/02/10. doi: 10.1038/nrg2719. PubMed PMID: 20142834; PubMed Central PMCID: PMCPMC3034103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Santos F, Dean W. Using immunofluorescence to observe methylation changes in mammalian preimplantation embryos. Methods Mol Biol. 2006;325:129-137. Epub 2006/06/10. doi: https://doi.org/10.1385/1-59745-005-7:129. PubMed PMID: 16761724.

  33. Cokus SJ, Feng S, Zhang X, Chen Z, Merriman B, Haudenschild CD, et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature. 2008;452(7184):215-9. Epub 2008/02/19. doi: 10.1038/nature06745. PubMed PMID: 18278030; PubMed Central PMCID: PMCPMC2377394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bocker MT, Tuorto F, Raddatz G, Musch T, Yang FC, Xu M, et al. Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster. Nat Commun. 2012;3:818. Epub 2012/05/10. doi: 10.1038/ncomms1826. PubMed PMID: 22569366; PubMed Central PMCID: PMCPMC3576573.

    Google Scholar 

  35. Gu H, Smith ZD, Bock C, Boyle P, Gnirke A, Meissner A. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nat Protoc. 2011;6(4):468-481. Epub 2011/03/18. doi: https://doi.org/10.1038/nprot.2010.190. PubMed PMID: 21412275.

    Article  CAS  PubMed  Google Scholar 

  36. Bonora G, Rubbi L, Morselli M, Ma F, Chronis C, Plath K, et al. DNA methylation estimation using methylation-sensitive restriction enzyme bisulfite sequencing (MREBS). PLoS One. 2019;14(4):e0214368. Epub 2019/04/05. doi: 10.1371/journal.pone.0214368. PubMed PMID: 30946758; PubMed Central PMCID: PMCPMC6448829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yu M, Hon GC, Szulwach KE, Song CX, Jin P, Ren B, et al. Tet-assisted bisulfite sequencing of 5-hydroxymethylcytosine. Nat Protoc. 2012;7(12):2159-70. Epub 2012/12/01. doi: 10.1038/nprot.2012.137. PubMed PMID: 23196972; PubMed Central PMCID: PMCPMC3641661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Treangen TJ, Salzberg SL. Repetitive DNA and next-generation sequencing: computational challenges and solutions. Nat Rev Genet. 2011;13(1):36-46. Epub 2011/11/30. doi: 10.1038/nrg3117. PubMed PMID: 22124482; PubMed Central PMCID: PMCPMC3324860.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. van der Maarel SM, Deidda G, Lemmers RJ, van Overveld PG, van der Wielen M, Hewitt JE, et al. De novo facioscapulohumeral muscular dystrophy: frequent somatic mosaicism, sex-dependent phenotype, and the role of mitotic transchromosomal repeat interaction between chromosomes 4 and 10. Am J Hum Genet. 2000;66(1):26-35. Epub 2000/01/13. doi: 10.1086/302730. PubMed PMID: 10631134; PubMed Central PMCID: PMCPMC1288331.

    Article  CAS  PubMed  Google Scholar 

  40. Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H, Peat J, et al. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods. 2014;11(8):817-20. Epub 2014/07/22. doi: 10.1038/nmeth.3035. PubMed PMID: 25042786; PubMed Central PMCID: PMCPMC4117646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, et al. Real-time DNA sequencing from single polymerase molecules. Science. 2009;323(5910):133-138. Epub 2008/11/22. doi: https://doi.org/10.1126/science.1162986. PubMed PMID: 19023044.

    Article  CAS  PubMed  Google Scholar 

  42. Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H. Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol. 2009;4(4):265-270. Epub 2009/04/08. doi: https://doi.org/10.1038/nnano.2009.12. PubMed PMID: 19350039.

    Article  CAS  PubMed  Google Scholar 

  43. Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, et al. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods. 2010;7(6):461-5. Epub 2010/05/11. doi: 10.1038/nmeth.1459. PubMed PMID: 20453866; PubMed Central PMCID: PMCPMC2879396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Jain M, Olsen HE, Paten B, Akeson M. The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community. Genome Biol. 2016;17(1):239. Epub 2016/11/27. doi: 10.1186/s13059-016-1103-0. PubMed PMID: 27887629; PubMed Central PMCID: PMCPMC5124260.

    Google Scholar 

  45. Chen Y, Wu Y, Liu L, Feng J, Zhang T, Qin S, et al. Study of the whole genome, methylome and transcriptome of Cordyceps militaris. Sci Rep. 2019;9(1):898. Epub 2019/01/31. doi: 10.1038/s41598-018-38021-4. PubMed PMID: 30696919; PubMed Central PMCID: PMCPMC6351555.

    Google Scholar 

  46. McIntyre ABR, Alexander N, Grigorev K, Bezdan D, Sichtig H, Chiu CY, et al. Single-molecule sequencing detection of N6-methyladenine in microbial reference materials. Nat Commun. 2019;10(1):579. Epub 2019/02/06. doi: 10.1038/s41467-019-08289-9. PubMed PMID: 30718479; PubMed Central PMCID: PMCPMC6362088.

    Google Scholar 

  47. Santos F, Hendrich B, Reik W, Dean W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol. 2002;241(1):172-182. Epub 2002/01/11. doi: https://doi.org/10.1006/dbio.2001.0501. PubMed PMID: 11784103.

    Article  CAS  PubMed  Google Scholar 

  48. Guo F, Li X, Liang D, Li T, Zhu P, Guo H, et al. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell. 2014;15(4):447-459. Epub 2014/09/16. doi: https://doi.org/10.1016/j.stem.2014.08.003. PubMed PMID: 25220291.

    Article  CAS  PubMed  Google Scholar 

  49. Shen L, Inoue A, He J, Liu Y, Lu F, Zhang Y. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell. 2014;15(4):459-71. Epub 2014/10/04. doi: 10.1016/j.stem.2014.09.002. PubMed PMID: 25280220; PubMed Central PMCID: PMCPMC4201500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang L, Zhang J, Duan J, Gao X, Zhu W, Lu X, et al. Programming and inheritance of parental DNA methylomes in mammals. Cell. 2014;157(4):979-91. Epub 2014/05/13. doi: 10.1016/j.cell.2014.04.017. PubMed PMID: 24813617; PubMed Central PMCID: PMCPMC4096154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Guo H, Zhu P, Yan L, Li R, Hu B, Lian Y, et al. The DNA methylation landscape of human early embryos. Nature. 2014;511(7511):606-610. Epub 2014/08/01. doi: https://doi.org/10.1038/nature13544. PubMed PMID: 25079557.

    Article  CAS  PubMed  Google Scholar 

  52. Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, et al. DNA methylation dynamics of the human preimplantation embryo. Nature. 2014;511(7511):611-5. Epub 2014/08/01. doi: 10.1038/nature13581. PubMed PMID: 25079558; PubMed Central PMCID: PMCPMC4178976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jiang L, Zhang J, Wang JJ, Wang L, Zhang L, Li G, et al. Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos. Cell. 2013;153(4):773-84. Epub 2013/05/15. doi: 10.1016/j.cell.2013.04.041. PubMed PMID: 23663777; PubMed Central PMCID: PMCPMC4081501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Potok ME, Nix DA, Parnell TJ, Cairns BR. Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern. Cell. 2013;153(4):759-72. Epub 2013/05/15. doi: 10.1016/j.cell.2013.04.030. PubMed PMID: 23663776; PubMed Central PMCID: PMCPMC4030421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Murphy PJ, Wu SF, James CR, Wike CL, Cairns BR. Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell. 2018;172(5):993-1006 e13. Epub 2018/02/20. doi: https://doi.org/10.1016/j.cell.2018.01.022. PubMed PMID: 29456083.

    Article  PubMed  CAS  Google Scholar 

  56. Ward WS, Coffey DS. DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells. Biol Reprod. 1991;44(4):569-574. Epub 1991/04/01. doi: https://doi.org/10.1095/biolreprod44.4.569. PubMed PMID: 2043729.

    Article  Google Scholar 

  57. 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. Epub 2009/06/16. doi: 10.1038/nature08162. PubMed PMID: 19525931; PubMed Central PMCID: PMCPMC2858064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wykes SM, Krawetz SA. The structural organization of sperm chromatin. J Biol Chem. 2003;278(32):29471-29477. Epub 2003/05/31. doi: https://doi.org/10.1074/jbc.M304545200. PubMed PMID: 12775710.

    Article  CAS  PubMed  Google Scholar 

  59. Falconer DS, Avery PJ. Variability of chimaeras and mosaics. J Embryol Exp Morphol. 1978;43:195-219. Epub 1978/02/01. PubMed PMID: 632737.

    Google Scholar 

  60. Gardner RL. The relationship between cell lineage and differentiation in the early mouse embryo. Results Probl Cell Differ. 1978;9:205-241. Epub 1978/01/01. PubMed PMID: 373038.

    Google Scholar 

  61. McMahon A, Fosten M, Monk M. Random X-chromosome inactivation in female primordial germ cells in the mouse. J Embryol Exp Morphol. 1981;64:251-258. Epub 1981/08/01. PubMed PMID: 7310304.

    Google Scholar 

  62. Ginsburg M, Snow MH, McLaren A. Primordial germ cells in the mouse embryo during gastrulation. Development. 1990;110(2):521-528. Epub 1990/10/01. PubMed PMID: 2133553.

    Google Scholar 

  63. Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, et al. Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002;117(1-2):15-23. Epub 2002/09/03. PubMed PMID: 12204247.

    Article  CAS  PubMed  Google Scholar 

  64. 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. Epub 2012/12/12. doi: 10.1016/j.molcel.2012.11.001. PubMed PMID: 23219530; PubMed Central PMCID: PMCPMC3533687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cowley M, Oakey RJ. Resetting for the next generation. Mol Cell. 2012;48(6):819-821. Epub 2013/01/01. doi: https://doi.org/10.1016/j.molcel.2012.12.007. PubMed PMID: 23273741.

    Article  CAS  PubMed  Google Scholar 

  66. Hackett JA, Sengupta R, Zylicz JJ, Murakami K, Lee C, Down TA, et al. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science. 2013;339(6118):448-52. Epub 2012/12/12. doi: 10.1126/science.1229277. PubMed PMID: 23223451; PubMed Central PMCID: PMCPMC3847602.

    Article  PubMed  CAS  Google Scholar 

  67. Guibert S, Forne T, Weber M. Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome research. 2012;22(4):633-41. Epub 2012/02/24. doi: 10.1101/gr.130997.111. PubMed PMID: 22357612; PubMed Central PMCID: PMCPMC3317146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A, Yayoi O, et al. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet. 2012;8(1):e1002440. Epub 2012/01/14. doi: 10.1371/journal.pgen.1002440. PubMed PMID: 22242016; PubMed Central PMCID: PMCPMC3252278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kobayashi H, Sakurai T, Miura F, Imai M, Mochiduki K, Yanagisawa E, et al. High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice. Genome research. 2013;23(4):616-27. Epub 2013/02/16. doi: 10.1101/gr.148023.112. PubMed PMID: 23410886; PubMed Central PMCID: PMCPMC3613579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tang WW, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR, et al. A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell. 2015;161(6):1453-67. Epub 2015/06/06. doi: 10.1016/j.cell.2015.04.053. PubMed PMID: 26046444; PubMed Central PMCID: PMCPMC4459712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Illum LRH, Bak ST, Lund S, Nielsen AL. DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line. J Mol Endocrinol. 2018;60(2):R39-R56. Epub 2017/12/06. doi: https://doi.org/10.1530/JME-17-0189. PubMed PMID: 29203518.

    Article  CAS  PubMed  Google Scholar 

  72. Hill PWS, Leitch HG, Requena CE, Sun Z, Amouroux R, Roman-Trufero M, et al. Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte. Nature. 2018;555(7696):392-6. Epub 2018/03/08. doi: 10.1038/nature25964. PubMed PMID: 29513657; PubMed Central PMCID: PMCPMC5856367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Baxter FA, Drake AJ. Non-genetic inheritance via the male germline in mammals. Philos Trans R Soc Lond B Biol Sci. 2019;374(1770):20180118. Epub 2019/04/11. doi: 10.1098/rstb.2018.0118. PubMed PMID: 30966887; PubMed Central PMCID: PMCPMC6460076.

    Article  CAS  Google Scholar 

  74. Heard E, Martienssen RA. Transgenerational epigenetic inheritance: myths and mechanisms. Cell. 2014;157(1):95-109. Epub 2014/04/01. doi: 10.1016/j.cell.2014.02.045. PubMed PMID: 24679529; PubMed Central PMCID: PMCPMC4020004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Daxinger L, Whitelaw E. Transgenerational epigenetic inheritance: more questions than answers. Genome research. 2010;20(12):1623-8. Epub 2010/11/03. doi: 10.1101/gr.106138.110. PubMed PMID: 21041414; PubMed Central PMCID: PMCPMC2989988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Daxinger L, Whitelaw E. Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet. 2012;13(3):153-162. Epub 2012/02/01. doi: https://doi.org/10.1038/nrg3188. PubMed PMID: 22290458.

    Article  CAS  PubMed  Google Scholar 

  77. Ost A, Lempradl A, Casas E, Weigert M, Tiko T, Deniz M, et al. Paternal diet defines offspring chromatin state and intergenerational obesity. Cell. 2014;159(6):1352-1364. Epub 2014/12/07. doi: https://doi.org/10.1016/j.cell.2014.11.005. PubMed PMID: 25480298.

    Article  PubMed  CAS  Google Scholar 

  78. de Castro Barbosa T, Alm PS, Krook A, Barres R, Zierath JR. Paternal high-fat diet transgenerationally impacts hepatic immunometabolism. FASEB J. 2019;33(5):6269-6280. Epub 2019/02/16. doi: https://doi.org/10.1096/fj.201801879RR. PubMed PMID: 30768368.

    Article  PubMed  Google Scholar 

  79. Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, et al. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J. 2013;27(10):4226-4243. Epub 2013/07/13. doi: https://doi.org/10.1096/fj.12-224048. PubMed PMID: 23845863.

    Article  CAS  PubMed  Google Scholar 

  80. Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature. 2010;467(7318):963-966. Epub 2010/10/22. doi: https://doi.org/10.1038/nature09491. PubMed PMID: 20962845.

    Article  CAS  PubMed  Google Scholar 

  81. Sarker G, Berrens R, von Arx J, Pelczar P, Reik W, Wolfrum C, et al. Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition. Translational psychiatry. 2018;8(1):195. Epub 2018/10/14. doi: 10.1038/s41398-018-0243-2. PubMed PMID: 30315171; PubMed Central PMCID: PMCPMC6185972.

    Google Scholar 

  82. Wei Y, Yang CR, Wei YP, Zhao ZA, Hou Y, Schatten H, et al. Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A. 2014;111(5):1873-8. Epub 2014/01/23. doi: 10.1073/pnas.1321195111. PubMed PMID: 24449870; PubMed Central PMCID: PMCPMC3918818.

    Article  CAS  Google Scholar 

  83. Huypens P, Sass S, Wu M, Dyckhoff D, Tschop M, Theis F, et al. Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nat Genet. 2016;48(5):497-499. Epub 2016/03/15. doi: https://doi.org/10.1038/ng.3527. PubMed PMID: 26974008.

    Article  CAS  PubMed  Google Scholar 

  84. Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell. 2010;143(7):1084-96. Epub 2010/12/25. doi: 10.1016/j.cell.2010.12.008. PubMed PMID: 21183072; PubMed Central PMCID: PMCPMC3039484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Peleg-Raibstein D, Sarker G, Litwan K, Kramer SD, Ametamey SM, Schibli R, et al. Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition. Translational psychiatry. 2016;6(10):e911. Epub 2016/10/05. doi: 10.1038/tp.2016.176. PubMed PMID: 27701408; PubMed Central PMCID: PMCPMC5315546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Radford EJ, Ito M, Shi H, Corish JA, Yamazawa K, Isganaitis E, et al. In utero effects. In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism. Science. 2014;345(6198):1255903. Epub 2014/07/12. doi: 10.1126/science.1255903. PubMed PMID: 25011554; PubMed Central PMCID: PMCPMC4404520.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Ferey JLA, Boudoures AL, Reid M, Drury A, Scheaffer S, Modi Z, et al. A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance. American journal of physiology Heart and circulatory physiology. 2019;316(5):H1202-H10. Epub 2019/03/23. doi: 10.1152/ajpheart.00013.2019. PubMed PMID: 30901280; PubMed Central PMCID: PMCPMC6580388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Pankey CL, Walton MW, Odhiambo JF, Smith AM, Ghnenis AB, Nathanielsz PW, et al. Intergenerational impact of maternal overnutrition and obesity throughout pregnancy in sheep on metabolic syndrome in grandsons and granddaughters. Domestic animal endocrinology. 2017;60:67-74. Epub 2017/05/22. doi: https://doi.org/10.1016/j.domaniend.2017.04.002. PubMed PMID: 28527530.

    Article  CAS  PubMed  Google Scholar 

  89. Sharma SS, Jangale NM, Harsulkar AM, Gokhale MK, Joshi BN. Chronic maternal calcium and 25-hydroxyvitamin D deficiency in Wistar rats programs abnormal hepatic gene expression leading to hepatic steatosis in female offspring. The Journal of nutritional biochemistry. 2017;43:36-46. Epub 2017/02/22. doi: https://doi.org/10.1016/j.jnutbio.2017.01.008. PubMed PMID: 28219837.

    Article  CAS  PubMed  Google Scholar 

  90. Zhu Y, Olsen SF, Mendola P, Halldorsson TI, Yeung EH, Granstrom C, et al. Maternal dietary intakes of refined grains during pregnancy and growth through the first 7 y of life among children born to women with gestational diabetes. The American journal of clinical nutrition. 2017;106(1):96-104. Epub 2017/06/09. doi: 10.3945/ajcn.116.136291. PubMed PMID: 28592607; PubMed Central PMCID: PMCPMC5486192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. An T, Zhang T, Teng F, Zuo JC, Pan YY, Liu YF, et al. Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity. Oncotarget. 2017;8(29):47876-89. Epub 2017/06/10. doi: 10.18632/oncotarget.18138. PubMed PMID: 28599310; PubMed Central PMCID: PMCPMC5564612.

    Google Scholar 

  92. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016;351(6271):397-400. Epub 2016/01/02. doi: https://doi.org/10.1126/science.aad7977. PubMed PMID: 26721680.

    Article  PubMed  CAS  Google Scholar 

  93. Fullston T, McPherson NO, Owens JA, Kang WX, Sandeman LY, Lane M. Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet. Physiological reports. 2015;3(3). Epub 2015/03/26. doi: 10.14814/phy2.12336. PubMed PMID: 25804263; PubMed Central PMCID: PMCPMC4393169.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Grandjean V, Fourre S, De Abreu DA, Derieppe MA, Remy JJ, Rassoulzadegan M. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders. Sci Rep. 2015;5:18193. Epub 2015/12/15. doi: 10.1038/srep18193. PubMed PMID: 26658372; PubMed Central PMCID: PMCPMC4677355.

    Google Scholar 

  95. 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. Epub 2016/01/02. doi: 10.1126/science.aad6780. PubMed PMID: 26721685; PubMed Central PMCID: PMCPMC4888079.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Shea JM, Serra RW, Carone BR, Shulha HP, Kucukural A, Ziller MJ, et al. Genetic and Epigenetic Variation, but Not Diet, Shape the Sperm Methylome. Dev Cell. 2015;35(6):750-8. Epub 2015/12/26. doi: 10.1016/j.devcel.2015.11.024. PubMed PMID: 26702833; PubMed Central PMCID: PMCPMC4691283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Cannon MV, Buchner DA, Hester J, Miller H, Sehayek E, Nadeau JH, et al. Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring. PLoS One. 2014;9(3):e90335. Epub 2014/03/07. doi: 10.1371/journal.pone.0090335. PubMed PMID: 24594983; PubMed Central PMCID: PMCPMC3940881.

    Article  PubMed  PubMed Central  CAS  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):345-352. Epub 2005/05/17. doi: https://doi.org/10.1016/j.reprotox.2005.04.005. PubMed PMID: 15893910.

    Article  CAS  PubMed  Google Scholar 

  99. Ravelli AC, van der Meulen JH, Michels RP, Osmond C, Barker DJ, Hales CN, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet (London, England). 1998;351(9097):173-7. Epub 1998/02/05. doi: 10.1016/s0140-6736(97)07244-9. PubMed PMID: 9449872.

    Article  CAS  Google Scholar 

  100. Veenendaal MV, Painter RC, de Rooij SR, Bossuyt PM, van der Post JA, Gluckman PD, et al. Transgenerational effects of prenatal exposure to the 1944-45 Dutch famine. BJOG: an international journal of obstetrics and gynaecology. 2013;120(5):548-553. Epub 2013/01/26. doi: https://doi.org/10.1111/1471-0528.12136. PubMed PMID: 23346894.

    Article  CAS  Google Scholar 

  101. Kaati G, Bygren LO, Edvinsson S. Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. European journal of human genetics: EJHG. 2002;10(11):682-688. Epub 2002/10/31. doi: https://doi.org/10.1038/sj.ejhg.5200859. PubMed PMID: 12404098.

    Article  CAS  PubMed  Google Scholar 

  102. Donkin I, Versteyhe S, Ingerslev LR, Qian K, Mechta M, Nordkap L, et al. Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. Cell Metab. 2016;23(2):369-378. Epub 2015/12/17. doi: https://doi.org/10.1016/j.cmet.2015.11.004. PubMed PMID: 26669700.

    Article  CAS  PubMed  Google Scholar 

  103. Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, et al. Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond). 2015;39(4):650-7. Epub 2013/10/26. doi: 10.1038/ijo.2013.193. PubMed PMID: 24158121; PubMed Central PMCID: PMCPMC4048324.

    Article  PubMed  CAS  Google Scholar 

  104. Ling C, Ronn T. Epigenetics in Human Obesity and Type 2 Diabetes. Cell Metab. 2019;29(5):1028-44. Epub 2019/04/16. doi: 10.1016/j.cmet.2019.03.009. PubMed PMID: 30982733; PubMed Central PMCID: PMCPMC6509280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Stenz L, Schechter DS, Serpa SR, Paoloni-Giacobino A. Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress. Current genomics. 2018;19(8):665-75. Epub 2018/12/12. doi: 10.2174/1389202919666171229145656. PubMed PMID: 30532646; PubMed Central PMCID: PMCPMC6225454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847-854. Epub 2004/06/29. doi: https://doi.org/10.1038/nn1276. PubMed PMID: 15220929.

    Article  CAS  PubMed  Google Scholar 

  107. Weaver IC, Champagne FA, Brown SE, Dymov S, Sharma S, Meaney MJ, et al. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J Neurosci. 2005;25(47):11045-11054. Epub 2005/11/25. doi: https://doi.org/10.1523/JNEUROSCI.3652-05.2005. PubMed PMID: 16306417.

    Article  CAS  PubMed  Google Scholar 

  108. Weaver IC, Meaney MJ, Szyf M. Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood. Proc Natl Acad Sci U S A. 2006;103(9):3480-5. Epub 2006/02/18. doi: 10.1073/pnas.0507526103. PubMed PMID: 16484373; PubMed Central PMCID: PMCPMC1413873.

    Article  CAS  Google Scholar 

  109. Franklin TB, Russig H, Weiss IC, Graff J, Linder N, Michalon A, et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry. 2010;68(5):408-415. Epub 2010/08/03. doi: https://doi.org/10.1016/j.biopsych.2010.05.036. PubMed PMID: 20673872.

    Article  PubMed  Google Scholar 

  110. Gapp K, Soldado-Magraner S, Alvarez-Sanchez M, Bohacek J, Vernaz G, Shu H, et al. Early life stress in fathers improves behavioural flexibility in their offspring. Nat Commun. 2014;5:5466. Epub 2014/11/19. doi: https://doi.org/10.1038/ncomms6466. PubMed PMID: 25405779.

  111. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, et al. Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci. 2014;17(5):667-9. Epub 2014/04/15. doi: 10.1038/nn.3695. PubMed PMID: 24728267; PubMed Central PMCID: PMCPMC4333222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Gapp K, Bohacek J, Grossmann J, Brunner AM, Manuella F, Nanni P, et al. Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma. Neuropsychopharmacology. 2016;41(11):2749-58. Epub 2016/06/10. doi: 10.1038/npp.2016.87. PubMed PMID: 27277118; PubMed Central PMCID: PMCPMC5026744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Morgan CP, Bale TL. Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage. J Neurosci. 2011;31(33):11748-55. Epub 2011/08/19. doi: 10.1523/JNEUROSCI.1887-11.2011. PubMed PMID: 21849535; PubMed Central PMCID: PMCPMC3164823.

    Article  CAS  PubMed  Google Scholar 

  114. Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci. 2013;33(21):9003-12. Epub 2013/05/24. doi: 10.1523/JNEUROSCI.0914-13.2013. PubMed PMID: 23699511; PubMed Central PMCID: PMCPMC3712504.

    Article  CAS  PubMed  Google Scholar 

  115. Dietz DM, Laplant Q, Watts EL, Hodes GE, Russo SJ, Feng J, et al. Paternal transmission of stress-induced pathologies. Biol Psychiatry. 2011;70(5):408-14. Epub 2011/06/18. doi: 10.1016/j.biopsych.2011.05.005. PubMed PMID: 21679926; PubMed Central PMCID: PMCPMC3217197.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci. 2014;17(1):89-96. Epub 2013/12/03. doi: 10.1038/nn.3594. PubMed PMID: 24292232; PubMed Central PMCID: PMCPMC3923835.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Magklara A, Yen A, Colquitt BM, Clowney EJ, Allen W, Markenscoff-Papadimitriou E, et al. An epigenetic signature for monoallelic olfactory receptor expression. Cell. 2011;145(4):555-70. Epub 2011/05/03. doi: 10.1016/j.cell.2011.03.040. PubMed PMID: 21529909; PubMed Central PMCID: PMCPMC3094500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Aoued HS, Sannigrahi S, Doshi N, Morrison FG, Linsenbaum H, Hunter SC, et al. Reversing Behavioral, Neuroanatomical, and Germline Influences of Intergenerational Stress. Biol Psychiatry. 2019;85(3):248-56. Epub 2018/10/08. doi: 10.1016/j.biopsych.2018.07.028. PubMed PMID: 30292395; PubMed Central PMCID: PMCPMC6326876.

    Article  PubMed  Google Scholar 

  119. Winther G, Eskelund A, Bay-Richter C, Elfving B, Muller HK, Lund S, et al. Grandmaternal high-fat diet primed anxiety-like behaviour in the second-generation female offspring. Behavioural brain research. 2019;359:47-55. Epub 2018/10/20. doi: https://doi.org/10.1016/j.bbr.2018.10.017. PubMed PMID: 30336180.

    Article  PubMed  Google Scholar 

  120. McCoy CR, Jackson NL, Day J, Clinton SM. Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala. Behavioural brain research. 2017;320:165-78. Epub 2016/12/15. doi: 10.1016/j.bbr.2016.12.008. PubMed PMID: 27965039; PubMed Central PMCID: PMCPMC5239722.

    Article  CAS  PubMed  Google Scholar 

  121. McCoy CR, Jackson NL, Brewer RL, Moughnyeh MM, Smith DL, Jr., Clinton SM. A paternal methyl donor depleted diet leads to increased anxiety- and depression-like behavior in adult rat offspring. Bioscience reports. 2018;38(4). Epub 2018/06/28. doi: 10.1042/BSR20180730. PubMed PMID: 29945927; PubMed Central PMCID: PMCPMC6153370.

    Google Scholar 

  122. Drobna 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(1):132-44. Epub 2017/11/23. doi: 10.1210/en.2017-00730. PubMed PMID: 29165653; PubMed Central PMCID: PMCPMC5761590.

    Article  PubMed Central  CAS  Google Scholar 

  123. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727):1466-1469. Epub 2005/06/04. doi: https://doi.org/10.1126/science.1108190. PubMed PMID: 15933200.

    Article  CAS  PubMed  Google Scholar 

  124. Guerrero-Bosagna C, Covert TR, Haque MM, Settles M, Nilsson EE, Anway MD, et al. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers. Reprod Toxicol. 2012;34(4):694-707. Epub 2012/10/09. doi: 10.1016/j.reprotox.2012.09.005. PubMed PMID: 23041264; PubMed Central PMCID: PMCPMC3513496.

    Article  CAS  PubMed  Google Scholar 

  125. Skinner MK, Nilsson E, Sadler-Riggleman I, Beck D, Ben Maamar M, McCarrey JR. Transgenerational sperm DNA methylation epimutation developmental origins following ancestral vinclozolin exposure. Epigenetics. 2019;14(7):721-39. Epub 2019/05/14. doi: 10.1080/15592294.2019.1614417. PubMed PMID: 31079544; PubMed Central PMCID: PMCPMC6557599.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Iqbal K, Tran DA, Li AX, Warden C, Bai AY, Singh P, et al. Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming. Genome Biol. 2015;16:59. Epub 2015/04/09. doi: 10.1186/s13059-015-0619-z. PubMed PMID: 25853433; PubMed Central PMCID: PMCPMC4376074.

    Google Scholar 

  127. Schneider S, Kaufmann W, Buesen R, van Ravenzwaay B. Vinclozolin--the lack of a transgenerational effect after oral maternal exposure during organogenesis. Reprod Toxicol. 2008;25(3):352-360. Epub 2008/05/20. doi: https://doi.org/10.1016/j.reprotox.2008.04.001. PubMed PMID: 18485663.

    Article  CAS  PubMed  Google Scholar 

  128. Schneider S, Marxfeld H, Groters S, Buesen R, van Ravenzwaay B. Vinclozolin--no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route. Reprod Toxicol. 2013;37:6-14. Epub 2013/01/15. doi: https://doi.org/10.1016/j.reprotox.2012.12.003. PubMed PMID: 23313085.

    Article  CAS  PubMed  Google Scholar 

  129. Latchney SE, Fields AM, Susiarjo M. Linking inter-individual variability to endocrine disruptors: insights for epigenetic inheritance. Mamm Genome. 2018;29(1-2):141-52. Epub 2017/12/09. doi: 10.1007/s00335-017-9729-0. PubMed PMID: 29218402; PubMed Central PMCID: PMCPMC5849504.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Nadeau JH. The nature of evidence for and against epigenetic inheritance. Genome Biol. 2015;16:137. Epub 2015/07/15. doi: 10.1186/s13059-015-0709-y. PubMed PMID: 26162370; PubMed Central PMCID: PMCPMC4499204.

    Google Scholar 

  131. Kubsad D, Nilsson EE, King SE, Sadler-Riggleman I, Beck D, Skinner MK. Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology. Sci Rep. 2019;9(1):6372. Epub 2019/04/24. doi: 10.1038/s41598-019-42860-0. PubMed PMID: 31011160; PubMed Central PMCID: PMCPMC6476885.

    Google Scholar 

  132. Yehuda R, Schmeidler J, Giller EL, Jr., Siever LJ, Binder-Brynes K. Relationship between posttraumatic stress disorder characteristics of Holocaust survivors and their adult offspring. The American journal of psychiatry. 1998;155(6):841-843. Epub 1998/06/10. doi: https://doi.org/10.1176/ajp.155.6.841. PubMed PMID: 9619162.

  133. Yehuda R, Teicher MH, Seckl JR, Grossman RA, Morris A, Bierer LM. Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of holocaust survivors. Archives of general psychiatry. 2007;64(9):1040-1048. Epub 2007/09/05. doi: https://doi.org/10.1001/archpsyc.64.9.1040. PubMed PMID: 17768269.

    Article  CAS  PubMed  Google Scholar 

  134. Yehuda R, Bierer LM. Transgenerational transmission of cortisol and PTSD risk. Progress in brain research. 2008;167:121-135. Epub 2007/11/27. doi: https://doi.org/10.1016/S0079-6123(07)67009-5. PubMed PMID: 18037011.

    Google Scholar 

  135. Yehuda R, Lehrner A, Bierer LM. The public reception of putative epigenetic mechanisms in the transgenerational effects of trauma. Environmental epigenetics. 2018;4(2):dvy018. Epub 2018/07/25. doi: 10.1093/eep/dvy018. PubMed PMID: 30038801; PubMed Central PMCID: PMCPMC6051458.

    Google Scholar 

  136. Lehrner A, Bierer LM, Passarelli V, Pratchett LC, Flory JD, Bader HN, et al. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors. Psychoneuroendocrinology. 2014;40:213-20. Epub 2014/02/04. doi: 10.1016/j.psyneuen.2013.11.019. PubMed PMID: 24485493; PubMed Central PMCID: PMCPMC3967845.

    Article  CAS  PubMed  Google Scholar 

  137. Yehuda R, Bell A, Bierer LM, Schmeidler J. Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors. Journal of psychiatric research. 2008;42(13):1104-11. Epub 2008/02/19. doi: 10.1016/j.jpsychires.2008.01.002. PubMed PMID: 18281061; PubMed Central PMCID: PMCPMC2612639.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Yehuda R, Daskalakis NP, Lehrner A, Desarnaud F, Bader HN, Makotkine I, et al. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. The American journal of psychiatry. 2014;171(8):872-80. Epub 2014/05/17. doi: 10.1176/appi.ajp.2014.13121571. PubMed PMID: 24832930; PubMed Central PMCID: PMCPMC4127390.

    Article  PubMed  Google Scholar 

  139. Bale TL. Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci. 2015;16(6):332-344. Epub 2015/04/30. doi: https://doi.org/10.1038/nrn3818. PubMed PMID: 25921815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Bohacek J, Mansuy IM. Molecular insights into transgenerational non-genetic inheritance of acquired behaviours. Nat Rev Genet. 2015;16(11):641-652. Epub 2015/09/30. doi: https://doi.org/10.1038/nrg3964. PubMed PMID: 26416311.

    Article  CAS  PubMed  Google Scholar 

  141. Fischer A. Epigenetic memory: the Lamarckian brain. EMBO J. 2014;33(9):945-67. Epub 2014/04/11. doi: 10.1002/embj.201387637. PubMed PMID: 24719207; PubMed Central PMCID: PMCPMC4193930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Dell PA, Rose FD. Transfer of effects from environmentally enriched and impoverished female rats to future offspring. Physiology & behavior. 1987;39(2):187-190. Epub 1987/01/01. PubMed PMID: 3575452.

    Google Scholar 

  143. Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7(9):697-709. Epub 2006/08/23. doi: https://doi.org/10.1038/nrn1970. PubMed PMID: 16924259.

    Article  CAS  PubMed  Google Scholar 

  144. Arai JA, Li S, Hartley DM, Feig LA. Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment. J Neurosci. 2009;29(5):1496-502. Epub 2009/02/06. doi: 10.1523/JNEUROSCI.5057-08.2009. PubMed PMID: 19193896; PubMed Central PMCID: PMCPMC3408235.

    Article  CAS  PubMed  Google Scholar 

  145. Benito E, Kerimoglu C, Ramachandran B, Pena-Centeno T, Jain G, Stilling RM, et al. RNA-Dependent Intergenerational Inheritance of Enhanced Synaptic Plasticity after Environmental Enrichment. Cell Rep. 2018;23(2):546-54. Epub 2018/04/12. doi: 10.1016/j.celrep.2018.03.059. PubMed PMID: 29642011; PubMed Central PMCID: PMCPMC5912949.

    Article  CAS  PubMed  Google Scholar 

  146. Ryan DP, Henzel KS, Pearson BL, Siwek ME, Papazoglou A, Guo L, et al. A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice. Molecular psychiatry. 2018;23(5):1345-55. Epub 2017/04/05. doi: 10.1038/mp.2017.53. PubMed PMID: 28373690; PubMed Central PMCID: PMCPMC5984088.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Zeybel M, Hardy T, Wong YK, Mathers JC, Fox CR, Gackowska A, et al. Multigenerational epigenetic adaptation of the hepatic wound-healing response. Nat Med. 2012;18(9):1369-77. Epub 2012/09/04. doi: 10.1038/nm.2893. PubMed PMID: 22941276; PubMed Central PMCID: PMCPMC3489975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Tucci V, Isles AR, Kelsey G, Ferguson-Smith AC, Erice Imprinting G. Genomic Imprinting and Physiological Processes in Mammals. Cell. 2019;176(5):952-965. Epub 2019/02/23. doi: https://doi.org/10.1016/j.cell.2019.01.043. PubMed PMID: 30794780.

    Article  CAS  PubMed  Google Scholar 

  149. Peters J. The role of genomic imprinting in biology and disease: an expanding view. Nat Rev Genet. 2014;15(8):517-530. Epub 2014/06/25. doi: https://doi.org/10.1038/nrg3766. PubMed PMID: 24958438.

    Article  CAS  PubMed  Google Scholar 

  150. Bartolomei MS, Ferguson-Smith AC. Mammalian genomic imprinting. Cold Spring Harb Perspect Biol. 2011;3(7). Epub 2011/05/18. doi: 10.1101/cshperspect.a002592. PubMed PMID: 21576252; PubMed Central PMCID: PMCPMC3119911.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Barlow DP, Bartolomei MS. Genomic imprinting in mammals. Cold Spring Harb Perspect Biol. 2014;6(2). Epub 2014/02/05. doi: 10.1101/cshperspect.a018382. PubMed PMID: 24492710; PubMed Central PMCID: PMCPMC3941233.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. McGrath J, Solter D. Nuclear transplantation in the mouse embryo by microsurgery and cell fusion. Science. 1983;220(4603):1300-1302. Epub 1983/06/17. doi: https://doi.org/10.1126/science.6857250. PubMed PMID: 6857250.

    Article  CAS  PubMed  Google Scholar 

  153. Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013;152(6):1308-1323. Epub 2013/03/19. doi: https://doi.org/10.1016/j.cell.2013.02.016. PubMed PMID: 23498939.

    Article  CAS  PubMed  Google Scholar 

  154. Cattanach BM, Jones J. Genetic imprinting in the mouse: implications for gene regulation. J Inherit Metab Dis. 1994;17(4):403-420. Epub 1994/01/01. PubMed PMID: 7967491.

    Article  CAS  PubMed  Google Scholar 

  155. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature. 1993;366(6453):362-365. Epub 1993/11/25. doi: https://doi.org/10.1038/366362a0. PubMed PMID: 8247133.

    Article  CAS  PubMed  Google Scholar 

  156. Fitzpatrick GV, Soloway PD, Higgins MJ. Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet. 2002;32(3):426-431. Epub 2002/11/01. doi: https://doi.org/10.1038/ng988. PubMed PMID: 12410230.

    Article  CAS  PubMed  Google Scholar 

  157. Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294(5551):2536-2539. Epub 2001/11/24. doi: https://doi.org/10.1126/science.1065848. PubMed PMID: 11719692.

    Article  CAS  PubMed  Google Scholar 

  158. Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004;429(6994):900-903. Epub 2004/06/25. doi: https://doi.org/10.1038/nature02633. PubMed PMID: 15215868.

    Article  CAS  PubMed  Google Scholar 

  159. Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A, et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011;43(8):811-4. Epub 2011/06/28. doi: 10.1038/ng.864. PubMed PMID: 21706000; PubMed Central PMCID: PMCPMC3146050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Sanchez-Delgado M, Court F, Vidal E, Medrano J, Monteagudo-Sanchez A, Martin-Trujillo A, et al. Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting. PLoS Genet. 2016;12(11):e1006427. Epub 2016/11/12. doi: 10.1371/journal.pgen.1006427. PubMed PMID: 27835649; PubMed Central PMCID: PMCPMC5106035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Nowak K, Stein G, Powell E, He LM, Naik S, Morris J, et al. Establishment of paternal allele-specific DNA methylation at the imprinted mouse Gtl2 locus. Epigenetics. 2011;6(8):1012-20. Epub 2011/07/05. doi: 10.4161/epi.6.8.16075. PubMed PMID: 21725202; PubMed Central PMCID: PMCPMC3359488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Sasaki H, Ferguson-Smith AC, Shum AS, Barton SC, Surani MA. Temporal and spatial regulation of H19 imprinting in normal and uniparental mouse embryos. Development. 1995;121(12):4195-4202. Epub 1995/12/01. PubMed PMID: 8575319.

    Google Scholar 

  163. Buiting K, Gross S, Lich C, Gillessen-Kaesbach G, el-Maarri O, Horsthemke B. Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am J Hum Genet. 2003;72(3):571-7. Epub 2003/01/25. doi: 10.1086/367926. PubMed PMID: 12545427; PubMed Central PMCID: PMCPMC1180233.

    Article  CAS  PubMed  Google Scholar 

  164. Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S, et al. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol Cell. 2011;44(3):361-72. Epub 2011/11/08. doi: 10.1016/j.molcel.2011.08.032. PubMed PMID: 22055183; PubMed Central PMCID: PMCPMC3210328.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, et al. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet. 2008;40(8):949-951. Epub 2008/07/16. doi: https://doi.org/10.1038/ng.187. PubMed PMID: 18622393.

    Article  CAS  PubMed  Google Scholar 

  166. Takahashi N, Coluccio A, Thorball CW, Planet E, Shi H, Offner S, et al. ZNF445 is a primary regulator of genomic imprinting. Genes Dev. 2019;33(1-2):49-54. Epub 2019/01/04. doi: 10.1101/gad.320069.118. PubMed PMID: 30602440; PubMed Central PMCID: PMCPMC6317318.

    Article  CAS  Google Scholar 

  167. Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, et al. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell. 2008;15(4):547-57. Epub 2008/10/16. doi: 10.1016/j.devcel.2008.08.014. PubMed PMID: 18854139; PubMed Central PMCID: PMCPMC2593089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Maenohara S, Unoki M, Toh H, Ohishi H, Sharif J, Koseki H, et al. Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. PLoS Genet. 2017;13(10):e1007042. Epub 2017/10/05. doi: 10.1371/journal.pgen.1007042. PubMed PMID: 28976982; PubMed Central PMCID: PMCPMC5643148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science. 2007;317(5845):1760-1764. Epub 2007/08/04. doi: https://doi.org/10.1126/science.1147939. PubMed PMID: 17673620.

    Article  CAS  PubMed  Google Scholar 

  170. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature. 2007;450(7171):908-912. Epub 2007/11/13. doi: https://doi.org/10.1038/nature06397. PubMed PMID: 17994007.

    Article  CAS  PubMed  Google Scholar 

  171. Andergassen D, Dotter CP, Wenzel D, Sigl V, Bammer PC, Muckenhuber M, et al. Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression. Elife. 2017;6. Epub 2017/08/15. doi: 10.7554/eLife.25125. PubMed PMID: 28806168; PubMed Central PMCID: PMCPMC5555720.

    Google Scholar 

  172. Perez JD, Rubinstein ND, Fernandez DE, Santoro SW, Needleman LA, Ho-Shing O, et al. Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain. Elife. 2015;4:e07860. Epub 2015/07/04. doi: 10.7554/eLife.07860. PubMed PMID: 26140685; PubMed Central PMCID: PMCPMC4512258.

    Google Scholar 

  173. Ge B, Pokholok DK, Kwan T, Grundberg E, Morcos L, Verlaan DJ, et al. Global patterns of cis variation in human cells revealed by high-density allelic expression analysis. Nat Genet. 2009;41(11):1216-1222. Epub 2009/10/20. doi: https://doi.org/10.1038/ng.473. PubMed PMID: 19838192.

    Article  CAS  PubMed  Google Scholar 

  174. Hasin-Brumshtein Y, Hormozdiari F, Martin L, van Nas A, Eskin E, Lusis AJ, et al. Allele-specific expression and eQTL analysis in mouse adipose tissue. BMC Genomics. 2014;15:471. Epub 2014/06/15. doi: 10.1186/1471-2164-15-471. PubMed PMID: 24927774; PubMed Central PMCID: PMCPMC4089026.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Onuchic V, Lurie E, Carrero I, Pawliczek P, Patel RY, Rozowsky J, et al. Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci. Science. 2018;361(6409). Epub 2018/08/25. doi: 10.1126/science.aar3146. PubMed PMID: 30139913; PubMed Central PMCID: PMCPMC6198826.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Dickies MM. A new viable yellow mutation in the house mouse. J Hered. 1962;53:84-86. Epub 1962/03/01. doi: https://doi.org/10.1093/oxfordjournals.jhered.a107129. PubMed PMID: 13886198.

    Article  CAS  PubMed  Google Scholar 

  177. Vasicek TJ, Zeng L, Guan XJ, Zhang T, Costantini F, Tilghman SM. Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics. 1997;147(2):777-86. Epub 1997/10/23. PubMed PMID: 9335612; PubMed Central PMCID: PMCPMC1208197.

    Google Scholar 

  178. 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):1463-1472. Epub 1994/06/15. doi: https://doi.org/10.1101/gad.8.12.1463. PubMed PMID: 7926745.

    Article  CAS  Google Scholar 

  179. Morgan HD, Sutherland HG, Martin DI, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23(3):314-318. Epub 1999/11/05. doi: https://doi.org/10.1038/15490. PubMed PMID: 10545949.

    Article  CAS  PubMed  Google Scholar 

  180. 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. Epub 2003/02/26. doi: 10.1073/pnas.0436776100. PubMed PMID: 12601169; PubMed Central PMCID: PMCPMC151376.

    Article  CAS  Google Scholar 

  181. Blewitt ME, Vickaryous NK, Paldi A, Koseki H, Whitelaw E. Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet. 2006;2(4):e49. Epub 2006/04/11. doi: 10.1371/journal.pgen.0020049. PubMed PMID: 16604157; PubMed Central PMCID: PMCPMC1428789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Dolinoy DC, Weinhouse C, Jones TR, Rozek LS, Jirtle RL. Variable histone modifications at the A(vy) metastable epiallele. Epigenetics. 2010;5(7):637-44. Epub 2010/07/31. doi: 10.4161/epi.5.7.12892. PubMed PMID: 20671424; PubMed Central PMCID: PMCPMC3052847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Cropley JE, Suter CM, Beckman KB, Martin DI. Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sci U S A. 2006;103(46):17308-12. Epub 2006/11/15. doi: 10.1073/pnas.0607090103. PubMed PMID: 17101998; PubMed Central PMCID: PMCPMC1838538.

    Article  CAS  Google Scholar 

  184. Kaminen-Ahola N, Ahola A, Maga M, Mallitt KA, Fahey P, Cox TC, et al. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 2010;6(1):e1000811. Epub 2010/01/20. doi: 10.1371/journal.pgen.1000811. PubMed PMID: 20084100; PubMed Central PMCID: PMCPMC2797299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  185. Wolff GL, Kodell RL, Moore SR, Cooney CA. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J. 1998;12(11):949-957. Epub 1998/08/26. PubMed PMID: 9707167.

    Google Scholar 

  186. Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect. 2006;114(4):567-72. Epub 2006/04/04. doi: 10.1289/ehp.8700. PubMed PMID: 16581547; PubMed Central PMCID: PMCPMC1440782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. 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. Epub 2007/08/03. doi: 10.1073/pnas.0703739104. PubMed PMID: 17670942; PubMed Central PMCID: PMCPMC1941790.

    Article  CAS  Google Scholar 

  188. Cropley JE, Suter CM, Beckman KB, Martin DI. CpG methylation of a silent controlling element in the murine Avy allele is incomplete and unresponsive to methyl donor supplementation. PLoS One. 2010;5(2):e9055. Epub 2010/02/09. doi: 10.1371/journal.pone.0009055. PubMed PMID: 20140227; PubMed Central PMCID: PMCPMC2816220.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. Smit AFA, Hubley R, Green P. RepeatMasker Open-4.0. http://wwwrepeatmaskerorg. 2013-2015.

    Google Scholar 

  190. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, et al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis. 2003;35(2):88-93. Epub 2003/01/21. doi: https://doi.org/10.1002/gene.10168. PubMed PMID: 12533790.

  191. Kazachenka A, Bertozzi TM, Sjoberg-Herrera MK, Walker N, Gardner J, Gunning R, et al. Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance. Cell. 2018;175(5):1259-71 e13. Epub 2018/11/21. doi: 10.1016/j.cell.2018.09.043. PubMed PMID: 30454646; PubMed Central PMCID: PMCPMC6242299.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Gueant JL, Chery C, Oussalah A, Nadaf J, Coelho D, Josse T, et al. APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients. Nat Commun. 2018;9(1):67. Epub 2018/01/06. doi: 10.1038/s41467-017-02306-5. PubMed PMID: 29302025; PubMed Central PMCID: PMCPMC5754367.

    Google Scholar 

  193. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76(1):1-18. Epub 2009/08/08. doi: 10.1111/j.1399-0004.2009.01230.x. PubMed PMID: 19659756; PubMed Central PMCID: PMCPMC2846640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Hitchins MP. The role of epigenetics in Lynch syndrome. Fam Cancer. 2013;12(2):189-205. Epub 2013/03/07. doi: https://doi.org/10.1007/s10689-013-9613-3. PubMed PMID: 23462881.

    Article  PubMed  Google Scholar 

  195. Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3’ exons of TACSTD1. Nat Genet. 2009;41(1):112-117. Epub 2008/12/23. doi: https://doi.org/10.1038/ng.283. PubMed PMID: 19098912.

    Article  PubMed  CAS  Google Scholar 

  196. Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG, et al. Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease. Nat Genet. 2003;34(2):157-165. Epub 2003/05/06. doi: https://doi.org/10.1038/ng1157. PubMed PMID: 12730694.

    Article  CAS  PubMed  Google Scholar 

  197. Hitchins MP, Wong JJ, Suthers G, Suter CM, Martin DI, Hawkins NJ, et al. Inheritance of a cancer-associated MLH1 germ-line epimutation. N Engl J Med. 2007;356(7):697-705. Epub 2007/02/16. doi: https://doi.org/10.1056/NEJMoa064522. PubMed PMID: 17301300.

    Article  CAS  PubMed  Google Scholar 

  198. Schaefer S, Nadeau JH. The Genetics of Epigenetic Inheritance: Modes, Molecules, and Mechanisms. Q Rev Biol. 2015;90(4):381-415. Epub 2015/12/31. PubMed PMID: 26714351.

    Article  PubMed  Google Scholar 

  199. Horsthemke B. A critical view on transgenerational epigenetic inheritance in humans. Nat Commun. 2018;9(1):2973. Epub 2018/08/01. doi: https://doi.org/10.1038/s41467-018-05445-5. PubMed PMID: 30061690; PubMed Central PMCID: PMCPMC6065375.

  200. van Otterdijk SD, Michels KB. Transgenerational epigenetic inheritance in mammals: how good is the evidence? FASEB J. 2016;30(7):2457-2465. Epub 2016/04/03. doi: https://doi.org/10.1096/fj.201500083. PubMed PMID: 27037350.

    Article  CAS  PubMed  Google Scholar 

  201. Chen Q, Yan W, Duan E. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat Rev Genet. 2016;17(12):733-43. Epub 2016/11/01. doi: 10.1038/nrg.2016.106. PubMed PMID: 27694809; PubMed Central PMCID: PMCPMC5441558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. 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):962-969. Epub 2008/06/10. doi: https://doi.org/10.1016/j.devcel.2008.03.009. PubMed PMID: 18539123.

    Article  CAS  PubMed  Google Scholar 

  203. Beckers J, Wurst W, de Angelis MH. Towards better mouse models: enhanced genotypes, systemic phenotyping and envirotype modelling. Nat Rev Genet. 2009;10(6):371-380. Epub 2009/05/13. doi: https://doi.org/10.1038/nrg2578. PubMed PMID: 19434078.

    Article  CAS  PubMed  Google Scholar 

  204. Xie N, Zhou Y, Sun Q, Tang B. Novel Epigenetic Techniques Provided by the CRISPR/Cas9 System. Stem Cells Int. 2018;2018:7834175. Epub 2018/08/21. doi: https://doi.org/10.1155/2018/7834175. PubMed PMID: 30123293; PubMed Central PMCID: PMCPMC6079388.

    Google Scholar 

  205. Vojta A, Dobrinic P, Tadic V, Bockor L, Korac P, Julg B, et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 2016;44(12):5615-5628. Epub 2016/03/13. doi: https://doi.org/10.1093/nar/gkw159. PubMed PMID: 26969735; PubMed Central PMCID: PMCPMC4937303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Huang YH, Su J, Lei Y, Brunetti L, Gundry MC, Zhang X, et al. DNA epigenome editing using CRISPR-Cas SunTag-directed DNMT3A. Genome Biol. 2017;18(1):176. Epub 2017/09/20. doi: https://doi.org/10.1186/s13059-017-1306-z. PubMed PMID: 28923089; PubMed Central PMCID: PMCPMC5604343.

  207. Morita S, Noguchi H, Horii T, Nakabayashi K, Kimura M, Okamura K, et al. Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions. Nat Biotechnol. 2016;34(10):1060-1065. Epub 2016/08/30. doi: https://doi.org/10.1038/nbt.3658. PubMed PMID: 27571369.

    Article  CAS  PubMed  Google Scholar 

  208. Liao HK, Hatanaka F, Araoka T, Reddy P, Wu MZ, Sui Y, et al. In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation. Cell. 2017;171(7):1495-1507 e15. Epub 2017/12/12. doi: https://doi.org/10.1016/j.cell.2017.10.025. PubMed PMID: 29224783; PubMed Central PMCID: PMCPMC5732045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  209. Wei Y, Lang J, Zhang Q, Yang CR, Zhao ZA, Zhang Y, et al. DNA methylation analysis and editing in single mammalian oocytes. Proc Natl Acad Sci U S A. 2019;116(20):9883-9892. Epub 2019/04/24. doi: https://doi.org/10.1073/pnas.1817703116. PubMed PMID: 31010926; PubMed Central PMCID: PMCPMC6525536.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Helmholtz Zentrum München GmbH, Institute of Experimental Genetics, Neuherberg, Germany

    Martin Irmler, Daniela Kaspar, Martin Hrabě de Angelis & Johannes Beckers

  2. Chair of Experimental Genetics, Technische Universität München, Freising, Germany

    Martin Hrabě de Angelis & Johannes Beckers

  3. Deutsches Zentrum für Diabetesforschung, Neuherberg, Germany

    Martin Hrabě de Angelis & Johannes Beckers

Authors
  1. Martin Irmler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Kaspar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Hrabě de Angelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johannes Beckers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johannes Beckers .

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

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

Irmler, M., Kaspar, D., Hrabě de Angelis, M., Beckers, J. (2020). The (not so) Controversial Role of DNA Methylation in Epigenetic Inheritance Across Generations. In: Teperino, R. (eds) Beyond Our Genes. Springer, Cham. https://doi.org/10.1007/978-3-030-35213-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation