CoChat
Sign Up
Cited by 589Epigenetics and DNA MethylationGenetic Syndromes and ImprintingChromosomal and Genetic Variations

Molecular mechanisms of transgenerational epigenetic inheritance

Open access
Fitz-James, Maximilian H., Cavalli, Giacomo·2022·Nature Reviews Genetics
DOI 10.1038/s41576-021-00438-5PMC PMC7619059
Open this paper in CoChat — free account

Abstract

Increasing evidence indicates that non-DNA sequence-based epigenetic information can be inherited across several generations in organisms ranging from yeast to plants to humans. This raises the possibility of heritable 'epimutations' contributing to heritable phenotypic variation and thus to evolution. Recent work has shed light on both the signals that underpin these epimutations, including DNA methylation, histone modifications and non-coding RNAs, and the mechanisms by which they are transmitted across generations at the molecular level. These mechanisms can vary greatly among species and have a more limited effect in mammals than in plants and other animal species. Nevertheless, common principles are emerging, with transmission occurring either via direct replicative mechanisms or indirect reconstruction of the signal in subsequent generations. As these processes become clearer we continue to improve our understanding of the distinctive features and relative contribution of DNA sequence and epigenetic variation to heritable differences in phenotype.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41576-021-00438-5

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increasing evidence indicates that epigenetic information can be inherited transgenerationally across a range of species, including humans, with effects manifesting in the F2 generation not subject to the original exposure.

    “Increasing evidence indicates that epigenetic information can also be inherited transgenerationally across a range of species, including humans, with effects manifesting in the F2 generation (i.e., in grandchildren) not subject to the original exposure.”

    From Ignoring the planet: A critical blind spot for research on ageing (2025) · cites this paper as [32]

    The Introduction reports robust evidence for transgenerational epigenetic inheritance in some model organisms, but says comprehensive evidence in mammals is scarce; the Conclusions state that robust evidence in humans is lacking. The Introduction also specifies that inheritance begins at F2 after paternal exposure, but at F3 after exposure of a pregnant female. The claim therefore overstates the evidence for humans and treats F2 as a universal threshold. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Epigenetic mechanisms support biological adaptability to environmental perturbations and can pass these adaptive responses to future generations.

    “Epigenetic mechanisms support biological adaptability to environmental perturbations and can pass these adaptive responses to future generations. This is in keeping with epigenetic intergenerational responses (IGRs) and transgenerational responses (TGRs) observed in humans and other mammals [31, 32].”

    From Ignoring the planet: A critical blind spot for research on ageing (2025) · cites this paper as [32]

    The review describes environmentally triggered phenotypes that can be inherited across generations (Mechanisms of epigenetic signal transmission, ‘Biophysical properties’; page not provided). But it explicitly leaves open whether those responses are adaptations or unintended consequences of environmental exposure. The claim presents their adaptive function as established. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 145

  1. [1]Cavalli G Heard E Advances in epigenetics link genetics to the environment and disease Nature 2019 571 489 499 31341302
  2. [2]Grewal SIS Klar AJS Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis Cell 1996 86 95 101 8689692
  3. [3]Ekwall K Olsson T Turner BM Cranston G Allshire RC Transient Inhibition of Histone Deacetylation Alters the Structural and Functional Imprint at Fission Yeast Centromeres effects (Turner et al Histones in heterochromatic regions in widely diver-gent species are consistently underacetylated. On mam-malian) Cell 1997 91 1021 1032 9428524
  4. [6]Heard E Martienssen Ra Transgenerational epigenetic inheritance: Myths and mechanisms Cell 2014 157 95 109 10.1016/j.cell.2014.02.045 24679529 PMC4020004 · DOI · Paper page
  5. [7]Skvortsova K Iovino N Bogdanović O Functions and mechanisms of epigenetic inheritance in animals Nat Rev Mol Cell Biol 2018 19 774 790 30425324
  6. [8]Perez MF Lehner B Intergenerational and transgenerational epigenetic inheritance in animals Nat Cell Biol 2019 21 143 151 30602724
  7. [9]Birney E Smith GD Greally JM Epigenome-wide Association Studies and the Interpretation of Disease-Omics PLoS Genet 2016 12 1 9 10.1371/journal.pgen.1006105 27336614 PMC4919098 · DOI
  8. [10]Lappalainen T Greally JM Associating cellular epigenetic models with human phenotypes Nat Rev Genet 2017 18 441 451 28555657
  9. [11]da Cruz RS Chen E Smith M Bates J de Assis S Diet and Transgenerational Epigenetic Inheritance of Breast Cancer: The Role of the Paternal Germline Front Nutr 2020 7 93 10.3389/fnut.2020.00093 32760734 PMC7373741 · DOI
  10. [12]King SE Skinner MK Epigenetic Transgenerational Inheritance of Obesity Susceptibility Trends Endocrinol Metab 2020 31 478 494 10.1016/j.tem.2020.02.009 32521235 PMC8260009 · DOI
  11. [13]Sarkies P Molecular mechanisms of epigenetic inheritance: Possible evolutionary implications Semin Cell Dev Biol 2020 97 106 115 A good review on the potential role of TEI in evolution and adaptation 10.1016/j.semcdb.2019.06.005 31228598 PMC6945114 · DOI
  12. [14]Bošković A Rando OJ Transgenerational epigenetic inheritance Annu Rev Genet 2018 52 21 41 30160987
  13. [15]Leroux S Embryonic environment and transgenerational effects in quail Genet Sel Evol 2017 49 14 10.1186/s12711-017-0292-7 28125975 PMC5270212 · DOI
  14. [16]Pierron F Transgenerational epigenetic sex determination: Environment experienced by female fish affects offspring sex ratio Environ Pollut 2021 277 116864 33714788
  15. [18]Bertozzi TM Ferguson-Smith AC Metastable epialleles and their contribution to epigenetic inheritance in mammals Semin Cell Dev Biol 2020 97 93 105 31551132
  16. [19]Kazachenka A Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance Cell 2018 175 1259 1271 e13 A screen for murine metastable epialleles identifying 87 candidates, although experimental validation shows that not all are involved in TEI 10.1016/j.cell.2018.11.017 30454646 PMC6242299 · DOI
  17. [20]Bertozzi TM Elmer JL Macfarlan TS Ferguson-Smith AC KRAB zinc finger protein diversification drives mammalian interindividual methylation variability Proc Natl Acad Sci U S A 2020 117 31290 31300 10.1073/pnas.2017053117 33239447 PMC7733849 · DOI
  18. [21]Schmitz RJ Patterns of population epigenomic diversity Nature 2013 495 193 198 10.1038/nature11968 23467092 PMC3798000 · DOI
  19. [22]Kawakatsu T Epigenomic Diversity in a Global Collection of Arabidopsis thaliana Accessions Cell 2016 166 492 505 10.1016/j.cell.2016.06.044 27419873 PMC5172462 · DOI
  20. [24]Cubas P An epigenetic mutation responsible for natural variation in floral symmetry Nature 1999 401 157 161 10490023
  21. [25]Manning K A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening Nat Genet 2006 38 948 952 16832354
  22. [26]Fujimoto R Evolution and Control of Imprinted FWA Genes in the Genus Arabidopsis PLoS Genet 2008 4 e1000048 10.1371/journal.pgen.1000048 18389059 PMC2270340 · DOI
  23. [27]Quadrana L Colot V Plant Transgenerational Epigenetics Annu Rev Genet 2016 50 467 491 27732791
  24. [28]Roux F Genome-wide epigenetic perturbation jump-starts patterns of heritable variation found in nature Genetics 2011 188 1015 1017 10.1534/genetics.111.128744 21596900 PMC3176100 · DOI
  25. [29]Furci L Identification and characterisation of hypomethylated DNA loci controlling quantitative resistance in Arabidopsis Elife 2019 8 e40655 Roux et al. (2011) and Furci at al. (2019) illustrate the likely widespread role of heritable DNA methylation in plant quantitative trait variation 10.7554/eLife.40655 30608232 PMC6342528 · DOI
  26. [30]Fanti L Piacentini L Cappucci U Casale AM Pimpinelli S Canalization by selection of de novo induced mutations Genetics 2017 206 1995 2006 10.1534/genetics.117.201079 28576865 PMC5560803 · DOI
  27. [32]Ciabrelli F Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila Nat Genet 2017 49 876 886 An intriguing example of a very stable epiallele in D. melanogaster that can be selected for both up- and down-regulation of a transgene, and which implicates H3K27me3 and 3D chromatin contacts 10.1038/ng.3848 28436983 PMC5484582 · DOI · Paper page
  28. [33]Rose NR Klose RJ Understanding the relationship between DNA methylation and histone lysine methylation Biochim Biophys Acta - Gene Regul Mech 2014 1839 1362 1372 10.1016/j.bbagrm.2014.02.007 24560929 PMC4316174 · DOI
  29. [34]Daxinger L Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype Sci Rep 2016 6 1 10 10.1038/srep25004 27112447 PMC4845014 · DOI
  30. [35]Torres-Garcia S Epigenetic gene silencing by heterochromatin primes fungal resistance Nature 2020 585 453 458 This study tracks the establishment of a heterochromatin-based epimutation in response to an environmental insult in fission yeast, providing evidence of TEI as an adaptation to a changing environment 10.1038/s41586-020-2706-x 32908306 PMC7116710 · DOI
  31. [37]Seong KH Li D Shimizu H Nakamura R Ishii S Inheritance of stress-induced, ATF-2-dependent epigenetic change Cell 2011 145 1049 1061 21703449
  32. [39]Greer EL Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans Nature 2010 466 383 387 10.1038/nature09195 20555324 PMC3075006 · DOI · Paper page
  33. [41]Lismer A Siklenka K Lafleur C Dumeaux V Kimmins S Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance Nucleic Acids Res 2020 48 11380 11393 10.1093/nar/gkaa712 33068438 PMC7672453 · DOI
  34. [42]Duempelmann L Skribbe M Bühler M Small RNAs in the Transgenerational Inheritance of Epigenetic Information Trends Genet 2020 36 203 214 31952840
  35. [43]Czech B piRNA-Guided Genome Defense: From Biogenesis to Silencing Annu Rev Genet 2018 52 131 157 10.1146/annurev-genet-120417-031441 30476449 PMC10784713 · DOI
  36. [44]Luteijn MJ Ketting RF PIWI-interacting RNAs: From generation to transgenerational epigenetics Nat Rev Genet 2013 14 523 534 23797853
  37. [47]Calo S A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides PLoS Genet 2017 13 1 26 10.1371/journal.pgen.1006686 28339467 PMC5384783 · DOI · Paper page
  38. [48]Gehring M Epigenetic dynamics during flowering plant reproduction: evidence for reprogramming? New Phytol 2019 224 91 96 10.1111/nph.15856 31002174 PMC6711810 · DOI
  39. [49]Calarco JP Reprogramming of DNA methylation in pollen guides epigenetic inheritance via small RNA Cell 2012 151 194 205 10.1016/j.cell.2012.09.001 23000270 PMC3697483 · DOI
  40. [50]Long J Nurse cell-–derived small RNAs define paternal epigenetic inheritance in Arabidopsis Science 2021 373 eabh0556 34210850
  41. [51]Cox DN A novel class of evolutionarily conserved genes defined by Genes Dev 1998 12 3715 3727 10.1101/gad.12.23.3715 9851978 PMC317255 · DOI
  42. [53]Le Thomas A Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state Genes Dev 2013 27 390 399 10.1101/gad.209841.112 23392610 PMC3589556 · DOI
  43. [54]Yu Y Panoramix enforces piRNA-dependent cotranscriptional silencing Science 2015 350 339 342 10.1126/science.aab0700 26472911 PMC4722808 · DOI
  44. [55]Mugat B The Mi-2 nucleosome remodeler and the Rpd3 histone deacetylase are involved in piRNA-guided heterochromatin formation Nat Commun 2020 11 2818 10.1038/s41467-020-16635-5 32499524 PMC7272611 · DOI
  45. [56]Klattenhoff C The Drosophila HP1 Homolog Rhino Is Required for Transposon Silencing and piRNA Production by Dual-Strand Clusters Cell 2009 138 1137 1149 10.1016/j.cell.2009.07.014 19732946 PMC2770713 · DOI
  46. [58]Rozhkov NV Small RNA-based silencing strategies for transposons in the process of invading Drosophila species Rna 2010 16 1634 1645 10.1261/rna.2217810 20581131 PMC2905761 · DOI
  47. [59]Le Thomas A Marinov GK Aravin AA A transgenerational process defines piRNA biogenesis in Drosophila virilis Cell Rep 2014 8 1617 1623 10.1016/j.celrep.2014.08.013 25199836 PMC5054749 · DOI
  48. [60]Grentzinger T PiRNA-mediated transgenerational inheritance of an acquired trait Genome Res 2012 22 1877 1888 10.1101/gr.136614.111 22555593 PMC3460183 · DOI · Paper page
  49. [61]Mao H The Nrde Pathway Mediates Small-RNA-Directed Histone H3 Lysine 27 Trimethylation in Caenorhabditis elegans Curr Biol 2015 25 2398 2403 26365259
  50. [62]Schwartz-Orbach L Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3 Elife 2020 9 e54309 10.7554/eLife.54309 32804637 PMC7431132 · DOI
  51. [63]Fire A Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Nature 1998 391 806 811 9486653
  52. [64]Vastenhouw NL Long-term gene silencing by RNAi Nature 2006 442 882 882 16929289
  53. [65]Ashe A PiRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans Cell 2012 150 88 99 10.1016/j.cell.2012.06.018 22738725 PMC3464430 · DOI · Paper page
  54. [66]Buckley BA A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality Nature 2012 489 447 451 10.1038/nature11352 22810588 PMC3509936 · DOI
  55. [67]Shirayama M PiRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline Cell 2012 150 65 77 10.1016/j.cell.2012.06.015 22738726 PMC3597741 · DOI
  56. [69]Rechavi O Starvation-induced transgenerational inheritance of small RNAs in C. elegans Cell 2014 158 277 287 10.1016/j.cell.2014.06.020 25018105 PMC4377509 · DOI · Paper page
  57. [70]Schott D Yanai I Hunter CP Natural RNA interference directs a heritable response to the environment Sci Rep 2015 4 7387 10.1038/srep07387 25552271 PMC4894413 · DOI
  58. [71]Kaletsky R C. elegans interprets bacterial non-coding RNAs to learn pathogenic avoidance Nature 2020 586 445 451 An intriguing case of an exogenous source of small RNAs triggering siRNA silencing of an endogenous neuronal gene over several generations in C. elegans 10.1038/s41586-020-2699-5 32908307 PMC8547118 · DOI
  59. [72]Posner R Neuronal Small RNAs Control Behavior Transgenerationally Cell 2019 177 1814 1826 10.1016/j.cell.2019.04.029 31178120 PMC6579485 · DOI
  60. [73]Almeida MV Andrade-Navarro MA Ketting RF Function and Evolution of Nematode RNAi Pathways Non-Coding RNA 2019 5 8 10.3390/ncrna5010008 30650636 PMC6468775 · DOI
  61. [74]Barucci G Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants Nat Cell Biol 2020 22 235 245 10.1038/s41556-020-0462-7 32015436 PMC7272227 · DOI
  62. [75]Quarato P Germline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos Nat Commun 2021 12 1441 10.1038/s41467-021-21691-6 33664268 PMC7933186 · DOI
  63. [76]Chen Q Yan W Duan E Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications Nat Rev Genet 2016 17 733 743 10.1038/nrg.2016.106 27694809 PMC5441558 · DOI · Paper page
  64. [77]Paris L Transgenerational inheritance of enhanced susceptibility to radiation-induced medulloblastoma in newborn Ptch1+/- mice after paternal irradiation Oncotarget 2015 6 36098 36112 10.18632/oncotarget.5553 26452034 PMC4742164 · DOI
  65. [78]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 9003 9012 10.1523/JNEUROSCI.0914-13.2013 23699511 PMC3712504 · DOI · Paper page
  66. [79]Fullston T 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 4226 4243 23845863
  67. [80]Gapp K Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice Nat Neurosci 2014 17 667 669 One of the first studies to show that injection of sperm ncRNAs can recapitulate behavioural phenotypes in another individual 10.1038/nn.3695 24728267 PMC4333222 · DOI · Paper page
  68. [81]Gapp K Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma Mol Psychiatry 2020 25 2162 2174 10.1038/s41380-018-0271-6 30374190 PMC7473836 · DOI · Paper page
  69. [82]Grandjean V RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders Sci Rep 2016 5 18193 10.1038/srep18193 26658372 PMC4677355 · DOI
  70. [85]Day JJ Sweatt JD DNA methylation and memory formation Nat Neurosci 2010 13 1319 1323 10.1038/nn.2666 20975755 PMC3130618 · DOI
  71. [87]Reverón-Gómez N Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication Mol Cell 2018 72 239 249 10.1016/j.molcel.2018.08.010 30146316 PMC6202308 · DOI
  72. [88]Escobar TM Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication Cell 2019 179 953 963 10.1016/j.cell.2019.10.009 31675501 PMC6917041 · DOI
  73. [89]Alabert C Domain Model Explains Propagation Dynamics and Stability of Histone H3K27 and H3K36 Methylation Landscapes Cell Rep 2020 30 1223 1234 31995760
  74. [90]O’Kane CJ Hyland EM Yeast epigenetics: The inheritance of histone modification states Biosci Rep 2019 39 1 13 10.1042/BSR20182006 30877183 PMC6504666 · DOI
  75. [91]Morgan HD Santos F Green K Dean W Reik W Epigenetic reprogramming in mammals Hum Mol Genet 2005 14 47 58 15809273
  76. [92]Nakamura T PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos Nature 2012 486 415 419 22722204
  77. [93]Li X A Maternal-Zygotic Effect Gene, Zfp57, Maintains Both Maternal and Paternal Imprints Dev Cell 2008 15 547 557 10.1016/j.devcel.2008.08.014 18854139 PMC2593089 · DOI
  78. [94]Messerschmidt DM Trim28 is required for epigenetic stability during mouse oocyte to embryo transition Science 2012 335 1499 1502 22442485
  79. [95]Lane N Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse Genesis 2003 35 88 93 12533790
  80. [96]Seisenberger S The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells Mol Cell 2012 48 849 862 10.1016/j.molcel.2012.11.001 23219530 PMC3533687 · DOI · Paper page
  81. [97]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 2 399 405 10.1371/journal.pgen.0020049 16604157 PMC1428789 · DOI
  82. [98]Fernandez-Gonzalez R Ramirez MA Pericuesta E Calle A Gutierrez-Adan A Histone modifications at the blastocyst Axin1Fu locus mark the heritability of in vitro culture-induced epigenetic alterations in mice Biol Reprod 2010 83 720 727 20650886
  83. [99]Gu L Wang Q Sun QY Histone modifications during mammalian oocyte maturation: Dynamics, regulation and functions Cell Cycle 2010 9 1942 1950 20436284
  84. [100]Hanna CW MLL2 conveys transcription-independent H3K4 trimethylation in oocytes Nat Struct Mol Biol 2018 25 73 82 29323282
  85. [101]Fraser R Lin C-J Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go! Reproduction 2016 152 R211 R222 10.1530/REP-16-0376 27601712 PMC5097126 · DOI
  86. [102]Wu J Chromatin analysis in human early development reveals epigenetic transition during ZGA Nature 2018 557 256 260 29720659
  87. [103]Liu B The landscape of RNA Pol II binding reveals a stepwise transition during ZGA Nature 2020 587 139 144 33116310
  88. [104]Gold HB Jung YH Corces VG Not just heads and tails: The complexity of the sperm epigenome J Biol Chem 2018 293 13815 13820 10.1074/jbc.R117.001561 29507096 PMC6130957 · DOI
  89. [105]Hammoud SS Distinctive chromatin in human sperm packages genes for embryo development Nature 2009 460 473 478 10.1038/nature08162 19525931 PMC2858064 · DOI
  90. [106]Brykczynska U Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa Nat Struct Mol Biol 2010 17 679 687 20473313
  91. [107]Jung YH Chromatin States in Mouse Sperm Correlate with Embryonic and Adult Regulatory Landscapes Cell Rep 2017 18 1366 1382 10.1016/j.celrep.2017.01.034 28178516 PMC5313040 · DOI
  92. [108]Wang L Programming and inheritance of parental DNA methylomes in mammals Cell 2014 157 979 991 10.1016/j.cell.2014.04.017 24813617 PMC4096154 · DOI
  93. [109]Kremsky I Corces VG Protection from DNA re-methylation by transcription factors in primordial germ cells and pre-implantation embryos can explain trans-generational epigenetic inheritance Genome Biol 2020 21 118 10.1186/s13059-020-02036-w 32423419 PMC7236515 · DOI
  94. [110]Tang F Maternal microRNAs are essential for mouse zygotic development Genes Dev 2007 21 644 648 10.1101/gad.418707 17369397 PMC1820938 · DOI
  95. [111]Tam OH Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes Nature 2008 453 534 538 10.1038/nature06904 18404147 PMC2981145 · DOI
  96. [112]Roovers EF Piwi proteins and piRNAs in Mammalian Oocytes and early embryos Cell Rep 2015 10 2069 2082 25818294
  97. [113]Watanabe T Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes Nature 2008 453 539 543 18404146
  98. [114]Brennecke J An Epigenetic Role for Maternally Inherited piRNAs in Transposon Silencing Science 2008 322 1387 1392 10.1126/science.1165171 19039138 PMC2805124 · DOI
  99. [115]Conine CC Sun F Song L Rivera-Pérez JA Rando OJ Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice Dev Cell 2018 46 470 480 10.1016/j.devcel.2018.06.024 30057276 PMC6103825 · DOI
  100. [116]Sharma U Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals Science 2016 351 391 396 10.1126/science.aad6780 26721685 PMC4888079 · DOI · Paper page
  101. [117]Zhang X Systematic identification and characterization of long non-coding RNAs in mouse mature sperm PLoS One 2017 12 e0173402 10.1371/journal.pone.0173402 28291811 PMC5349675 · DOI
  102. [118]Lev I Rechavi O Germ Granules Allow Transmission of Small RNA-Based Parental Responses in the ‘“ Germ Plasm ”’ ISCIENCE 2020 23 101831 10.1016/j.isci.2020.101831 33305186 PMC7718480 · DOI
  103. [119]Dodson AE Kennedy SK Germ Granules Coordinate RNA-based Epigenetic Inheritance Pathways Dev Cell 2019 50 704 715 10.1016/j.devcel.2019.07.025 31402284 PMC7316138 · DOI
  104. [120]Lev I Germ Granules Govern Small RNA Inheritance Curr Biol 2019 29 2880 2891 Dodson et al. (2019) and Lev et al. (2019) show the involvement of germ granules in small RNA inheritance and TEI in C. elegans 10.1016/j.cub.2019.07.054 31378614 PMC6739422 · DOI
  105. [121]Voronina E Seydoux G Sassone-Corsi P Nagamori I RNA Granules in Germ Cells Cold Spring Harb Perspect Biol 2011 3 a002774–a002774 10.1101/cshperspect.a002774 21768607 PMC3225947 · DOI
  106. [122]Banani SF Lee HO Hyman AA Rosen MK Biomolecular condensates: Organizers of cellular biochemistry Nat Rev Mol Cell Biol 2017 18 285 298 10.1038/nrm.2017.7 28225081 PMC7434221 · DOI
  107. [123]Dodson AE Kennedy S Phase Separation in Germ Cells and Development Dev Cell 2020 55 4 17 10.1016/j.devcel.2020.09.004 33007213 PMC7572804 · DOI
  108. [124]Bonev B Cavalli G Organization and function of the 3D genome Nat Rev Genet 2016 17 661 678 27739532
  109. [125]van Steensel B Belmont AS Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression Cell 2017 169 780 791 10.1016/j.cell.2017.04.022 28525751 PMC5532494 · DOI · Paper page
  110. [126]Robson MI Tissue-Specific Gene Repositioning by Muscle Nuclear Membrane Proteins Enhances Repression of Critical Developmental Genes during Myogenesis Mol Cell 2016 62 834 847 10.1016/j.molcel.2016.04.035 27264872 PMC4914829 · DOI
  111. [127]Holla S Positioning Heterochromatin at the Nuclear Periphery Suppresses Histone Turnover to Promote Epigenetic Inheritance Cell 2020 180 150 164 10.1016/j.cell.2019.12.004 31883795 PMC7102895 · DOI
  112. [128]Sun J Shi Y Yildirim E The Nuclear Pore Complex in Cell Type-Specific Chromatin Structure and Gene Regulation Trends Genet 2019 35 579 588 31213386
  113. [129]Schuettengruber B Bourbon HM Di Croce L Cavalli G Genome Regulation by Polycomb and Trithorax: 70 Years and Counting Cell 2017 171 34 57 28938122
  114. [132]Jung YH Recruitment of CTCF to an Fto enhancer is responsible for transgenerational inheritance of obesity bioRxiv 2021 1 48 10.1073/pnas.2214988119 36469784 PMC9897486 · DOI
  115. [133]Loos RJF Yeo GSH The bigger picture of FTO - The first GWAS-identified obesity gene Nat Rev Endocrinol 2014 10 51 61 10.1038/nrendo.2013.227 24247219 PMC4188449 · DOI
  116. [134]Hollick JB Paramutation and related phenomena in diverse species Nat Rev Genet 2016 18 5 23 A good review on paramutation with a focus on plants, but touching on other organisms as well 27748375
  117. [135]Pilu R Paramutation phenomena in plants Semin Cell Dev Biol 2015 44 2 10 26335267
  118. [136]Luteijn MJ Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans EMBO J 2012 31 3422 30 10.1038/emboj.2012.213 22850670 PMC3419935 · DOI
  119. [137]De Vanssay A Paramutation in Drosophila linked to emergence of a piRNA-producing locus Nature 2012 490 112 115 22922650
  120. [138]Hermant C Paramutation in drosophila requires both nuclear and cytoplasmic actors of the piRNA pathway and induces cis-spreading of piRNA production Genetics 2015 201 1381 1396 10.1534/genetics.115.180307 26482790 PMC4676525 · DOI
  121. [139]Rassoulzadegan M RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse Nature 2006 441 469 474 16724059
  122. [140]Wagner KD RNA Induction and Inheritance of Epigenetic Cardiac Hypertrophy in the Mouse Dev Cell 2008 14 962 969 18539123
  123. [141]Yuan S Oliver D Schuster A Zheng H Yan W Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice Sci Rep 2015 5 9266 10.1038/srep09266 25783852 PMC4363887 · DOI
  124. [142]Ronsseray S Paramutation phenomena in non-vertebrate animals Semin Cell Dev Biol 2015 44 39 46 26318740
  125. [143]Apte MS Meller VH Homologue Pairing in Flies and Mammals: Gene Regulation When Two Are Involved Genet Res Int 2012 2012 430587 10.1155/2012/430587 22567388 PMC3335585 · DOI
  126. [144]Fukaya T Levine M Transvection Curr Biol 2017 27 R1047 R1049 10.1016/j.cub.2017.08.001 29017034 PMC6092964 · DOI
  127. [145]Hoencamp C 3D genomics across the tree of life reveals condensin II as a determinant of architecture type Science 2021 372 984 989 10.1126/science.abe2218 34045355 PMC8172041 · DOI
  128. [146]Bente H Foerster AM Lettner N Mittelsten Scheid O Polyploidy-associated paramutation in Arabidopsis is determined by small RNAs, temperature, and allele structure PLOS Genet 2021 17 e1009444 10.1371/journal.pgen.1009444 33690630 PMC7978347 · DOI
  129. [147]Thorson JLM Beck D Ben Maamar M Nilsson EE Skinner MK Ancestral plastics exposure induces transgenerational disease-specific sperm epigenome-wide association biomarkers Environ Epigenetics 2021 7 dvaa023 10.1093/eep/dvaa023 33841921 PMC8022921 · DOI
  130. [148]Silveira AB Extensive Natural Epigenetic Variation at a De Novo Originated Gene PLoS Genet 2013 9 e1003437 10.1371/journal.pgen.1003437 23593031 PMC3623765 · DOI
  131. [149]Alonso C Pérez R Bazaga P Medrano M Herrera CM I ndividual variation in size and fecundity is correlated with differences in global DNA cytosine methylation in the perennial herb Helleborus foetidus (Ranunculaceae) Am J Bot 2014 101 1309 1313 25143467
  132. [150]Skinner MK Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease Epigenetics Chromatin 2018 11 8 10.1186/s13072-018-0178-0 29482626 PMC5827984 · DOI
  133. [151]Greer EL Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans Nature 2011 479 365 371 10.1038/nature10572 22012258 PMC3368121 · DOI · Paper page
  134. [152]Bogdanović O Veenstra GJC DNA methylation and methyl-CpG binding proteins: Developmental requirements and function Chromosoma 2009 118 549 565 10.1007/s00412-009-0221-9 19506892 PMC2729420 · DOI
  135. [153]Zhang H Lang Z Zhu JK Dynamics and function of DNA methylation in plants Nat Rev Mol Cell Biol 2018 19 489 506 29784956
  136. [155]Murphy PJ Wu SF James CR Wike CL Cairns BR Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming Cell 2018 172 993 1006 29456083
  137. [156]Martire S Banaszynski LA The roles of histone variants in fine-tuning chromatin organization and function Nat Rev Mol Cell Biol 2020 21 522 541 10.1038/s41580-020-0262-8 32665685 PMC8245300 · DOI · Paper page
  138. [158]Allshire RC Madhani HD Ten principles of heterochromatin formation and function Nat Rev Mol Cell Biol 2018 19 229 244 10.1038/nrm.2017.119 29235574 PMC6822695 · DOI
  139. [159]Kim J Kim H Recruitment and biological consequences of histone modification of H3K27me3 and H3K9me3 ILAR J 2012 53 232 9 10.1093/ilar.53.3-4.232 23744963 PMC3747788 · DOI
  140. [160]Blackledge NP Rose NR Klose RJ Targeting Polycomb systems to regulate gene expression: modifications to a complex story Nat Rev Mol Cell Biol 2015 16 643 649 10.1038/nrm4067 26420232 PMC5469428 · DOI
  141. [162]Xiao M MicroRNAs activate gene transcription epigenetically as an enhancer trigger RNA Biol 2017 14 1326 1334 10.1080/15476286.2015.1112487 26853707 PMC5711461 · DOI
  142. [164]Nishi K Nishi A Nagasawa T Ui-Tei K Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus Rna 2013 19 17 35 10.1261/rna.034769.112 23150874 PMC3527724 · DOI · Paper page
  143. [165]Benhamed M Herbig U Ye T Dejean A Bischof O Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells Nat Cell Biol 2012 14 266 275 10.1038/ncb2443 22366686 PMC5423543 · DOI · Paper page
  144. [166]Schmitz SU Grote P Herrmann BG Mechanisms of long noncoding RNA function in development and disease Cell Mol Life Sci 2016 73 2491 2509 10.1007/s00018-016-2174-5 27007508 PMC4894931 · DOI
  145. [167]Peng H A novel class of tRNA-derived small RNAs extremely enriched in mature mouse sperm Cell Res 2012 22 1609 1612 10.1038/cr.2012.141 23044802 PMC3494397 · DOI

Cited by

Sorted by citations

Authors
Fitz-James, M. H., & Cavalli, G.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Cavalli, Giacomo
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2022-01-04
Volume
23
Issue
6
Pages
325-341
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/s41576-021-00438-5
PMC
PMC7619059
OpenAlex
W4206179351
Cited by
589
References
22
Citations by year
2026: 110 · 2025: 168 · 2024: 144 · 2023: 122 · 2022: 44 · 2021: 1
FWCI
12.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • PubMed Central (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
transgenerational epigenetic inheritance, epimutations, DNA methylation, histone modifications, non-coding RNA, epigenetic inheritance, heritable phenotypic variation, evolution, epigenetic variation, DNA sequence variation
MeSH terms
Animals, Mammals, DNA Methylation, Databases, Genetic, Inheritance Patterns, Epigenesis, Genetic, Epigenomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review