Epigenetic Phenomenon of Paramutation in Plants and Animals (Review)

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The phenomenon of paramutation describes the interaction between two alleles, in which one allele initiates inherited epigenetic conversion of another allele without affecting the DNA sequence. Epigenetic transformations due to paramutation are accompanied by a change in the DNA and/or histone methylation patterns, affecting gene expression. Studies of paramutation in plants and animals have identified small non-coding RNAs as the main effector molecules required for the initiation of epigenetic changes in gene loci. Due to the fact that small non-coding RNAs can be transmitted across generations, the paramutation effect can be inherited and maintained in a population. In this review, we will systematically analyse the examples of paramutation in different living systems described so far, highlighting common and different molecular and genetic aspects of paramutation between organisms, and consider the role of this phenomenon in evolution.

Full Text

Restricted Access

About the authors

D. A. Kulikova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Koltzov Institute of Developmental Biology, Russian Academy of Sciences

Email: sergeifunikov@mail.ru
Russian Federation, 119991 Moscow; 119334 Moscow

A. V. Bespalova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: sergeifunikov@mail.ru
Russian Federation, 119991 Moscow

E. S. Zelentsova

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: sergeifunikov@mail.ru
Russian Federation, 119991 Moscow

M. B. Evgen’ev

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: sergeifunikov@mail.ru
Russian Federation, 119991 Moscow

S. Yu. Funikov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Author for correspondence.
Email: sergeifunikov@mail.ru
Russian Federation, 119991 Moscow

References

  1. Hollick, J. B. (2017) Paramutation and related phenomena in diverse species, Nat. Rev. Genet., 18, 5-23, https://doi.org/10.1038/nrg.2016.115.
  2. Ronsseray, S. (2015) Paramutation phenomena in non-vertebrate animals, Semin. Cell Dev. Biol., 44, 39-46, https://doi.org/10.1016/j.semcdb.2015.08.009.
  3. Pilu, R. (2015) Paramutation phenomena in plants, Semin. Cell Dev. Biol., 44, 2-10, https://doi.org/10.1016/j.semcdb.2015.08.015.
  4. Chandler, V. L. (2007) Paramutation: from maize to mice, Cell, 128, 641-645, https://doi.org/10.1016/j.cell.2007.02.007.
  5. Bateson, W., and Pellew, C. (1915) On the genetics of “Rogues” among culinary peas (Pisum sativum), J. Genetics, 5, 13-36, https://doi.org/10.1007/BF02982150.
  6. Brink, R. A. (1958) Paramutation at the R locus in maize, Cold Spring Harb. Symp. Quantitat. Biol., 23, 379-391, https://doi.org/10.1101/sqb.1958.023.01.036.
  7. Brink, R. A. (1956) A genetic change associated with the R locus in maize which is directed and potentially reversible, Genetics, 41, 872-889, https://doi.org/10.1093/genetics/41.6.872.
  8. Hagemann, R. (1969) Somatic conversion (paramutation) at the sulfurea locus of Lycopersicon esculentum Mill. III. studies with trisomics, Can. J. Genet. Cytol., 11, 346-358, https://doi.org/10.1139/g69-043.
  9. Renner, O. (1959) Somatic conversion in the heredity of the Cruciata character in Œnothera, Heredity, 13, 283-288, https://doi.org/10.1038/hdy.1959.35.
  10. Pilu, R., Panzeri, D., Cassani, E., Cerino Badone, F., Landoni, M., and Nielsen, E. (2009) A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait, Heredity (Edinb), 102, 236-245, https://doi.org/10.1038/hdy.2008.96.
  11. Shi, J., Wang, H., Schellin, K., Li, B., Faller, M., Stoop, J. M., Meeley, R. B., Ertl, D. S., Ranch, J. P., and Glassman, K. (2007) Embryo-specific silencing of a transporter reduces phytic acid content of maize and soybean seeds, Nat. Biotechnol., 25, 930-937, https://doi.org/10.1038/nbt1322.
  12. Coe, E. H. (1966) The properties, origin, and mechanism of conversion-type inheritance at the B locus in maize, Genetics, 53, 1035-1063, https://doi.org/10.1093/genetics/53.6.1035.
  13. Patterson, G. I., Kubo, K. M., Shroyer, T., and Chandler, V. L. (1995) Sequences required for paramutation of the maize b gene map to a region containing the promoter and upstream sequences, Genetics, 140, 1389-1406, https://doi.org/10.1093/genetics/140.4.1389.
  14. Matzke, M. A., and Mosher, R. A. (2014) RNA-directed DNA methylation: an epigenetic pathway of increasing complexity, Nat. Rev. Genet., 15, 394-408, https://doi.org/10.1038/nrg3683.
  15. Zhong, X., Du, J., Hale, C. J., Gallego-Bartolome, J., Feng, S., Vashisht, A. A., Chory, J., Wohlschlegel, J. A., Patel, D. J., and Jacobsen, S. E. (2014) Molecular mechanism of action of plant DRM de novo DNA methyltransferases, Cell, 157, 1050-1060, https://doi.org/10.1016/j.cell.2014.03.056.
  16. Mette, M. F., Aufsatz, W., van der Winden, J., Matzke, M. A., and Matzke, A. J. (2000) Transcriptional silencing and promoter methylation triggered by double-stranded RNA, EMBO J., 19, 5194-5201, https://doi.org/10.1093/emboj/19.19.5194.
  17. Erdmann, R. M., and Picard, C. L. (2020) RNA-directed DNA methylation, PLoS Genet., 16, e1009034, https://doi.org/10.1371/journal.pgen.1009034.
  18. Chow, H. T., and Mosher, R. A. (2023) Small RNA-mediated DNA methylation during plant reproduction, Plant Cell, 35, 1787-1800, https://doi.org/10.1093/plcell/koad010.
  19. Akinmusola, R. Y., Wilkins, C. A., and Doughty, J. (2023) DDM1-mediated TE silencing in plants, Plants (Basel), 12, https://doi.org/10.3390/plants12030437.
  20. Cuerda-Gil, D., and Slotkin, R. K. (2016) Non-canonical RNA-directed DNA methylation, Nat. Plants, 2, 16163, https://doi.org/10.1038/nplants.2016.163.
  21. Svoboda, P. (2014) Renaissance of mammalian endogenous RNAi, FEBS Lett., 588, 2550-2556, https://doi.org/10.1016/j.febslet.2014.05.030.
  22. Lahmy, S., Bies-Etheve, N., and Lagrange, T. (2010) Plant-specific multisubunit RNA polymerase in gene silencing, Epigenetics, 5, 4-8, https://doi.org/10.4161/epi.5.1.10435.
  23. Tucker, S. L., Reece, J., Ream, T. S., and Pikaard, C. S. (2010) Evolutionary history of plant multisubunit RNA polymerases IV and V: subunit origins via genome-wide and segmental gene duplications, retrotransposition, and lineage-specific subfunctionalization, Cold Spring Harb. Symp. Quantitat. Biol., 75, 285-297, https://doi.org/10.1101/sqb.2010.75.037.
  24. Onodera, Y., Haag, J. R., Ream, T., Costa Nunes, P., Pontes, O., and Pikaard, C. S. (2005) Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation, Cell, 120, 613-622, https://doi.org/10.1016/j.cell.2005.02.007.
  25. Kanno, T., Huettel, B., Mette, M. F., Aufsatz, W., Jaligot, E., Daxinger, L., Kreil, D. P., Matzke, M., and Matzke, A. J. (2005) Atypical RNA polymerase subunits required for RNA-directed DNA methylation, Nat. Genet., 37, 761-765, https://doi.org/10.1038/ng1580.
  26. Alleman, M., Sidorenko, L., McGinnis, K., Seshadri, V., Dorweiler, J. E., White, J., Sikkink, K., and Chandler, V. L. (2006) An RNA-dependent RNA polymerase is required for paramutation in maize, Nature, 442, 295-298, https://doi.org/10.1038/nature04884.
  27. Zhou, M., Palanca, A. M. S., and Law, J. A. (2018) Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family, Nat. Genet., 50, 865-873, https://doi.org/10.1038/s41588-018-0115-y.
  28. Law, J. A., Du, J., Hale, C. J., Feng, S., Krajewski, K., Palanca, A. M., Strahl, B. D., Patel, D. J., and Jacobsen, S. E. (2013) Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1, Nature, 498, 385-389, https://doi.org/10.1038/nature12178.
  29. Zhang, H., He, X., and Zhu, J. K. (2013) RNA-directed DNA methylation in plants: where to start? RNA Biol., 10, 1593-1596, https://doi.org/10.4161/rna.26312.
  30. Loffer, A., Singh, J., Fukudome, A., Mishra, V., Wang, F., and Pikaard, C. S. (2022) A DCL3 dicing code within Pol IV–RDR2 transcripts diversifies the siRNA pool guiding RNA-directed DNA methylation, eLife, 11, https://doi.org/10.7554/eLife.73260.
  31. Wang, Q., Xue, Y., Zhang, L., Zhong, Z., Feng, S., Wang, C., Xiao, L., Yang, Z., Harris, C. J., Wu, Z., Zhai, J., Yang, M., Li, S., Jacobsen, S. E., and Du, J. (2021) Mechanism of siRNA production by a plant Dicer–RNA complex in dicing-competent conformation, Science, 374, 1152-1157, https://doi.org/10.1126/science.abl4546.
  32. Yang, Z., Ebright, Y. W., Yu, B., and Chen, X. (2006) HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2′ OH of the 3′ terminal nucleotide, Nucleic Acids Res., 34, 667-675, https://doi.org/10.1093/nar/gkj474.
  33. Panda, K., and Slotkin, R. K. (2013) Proposed mechanism for the initiation of transposable element silencing by the RDR6-directed DNA methylation pathway, Plant Signal. Behav., 8, https://doi.org/10.4161/psb.25206.
  34. Xie, M., and Yu, B. (2015) siRNA-directed DNA methylation in plants, Curr. Genomics, 16, 23-31, https://doi.org/10.2174/1389202915666141128002211.
  35. Vaucheret, H. (2008) Plant argonautes, Trends Plant Sci., 13, 350-358, https://doi.org/10.1016/j.tplants.2008.04.007.
  36. Havecker, E. R., Wallbridge, L. M., Hardcastle, T. J., Bush, M. S., Kelly, K. A., Dunn, R. M., Schwach, F., Doonan, J. H., and Baulcombe, D. C. (2010) The Arabidopsis RNA-directed DNA methylation argonautes functionally diverge based on their expression and interaction with target loci, Plant Cell, 22, 321-334, https://doi.org/10.1105/tpc.109.072199.
  37. Wierzbicki, A. T., Haag, J. R., and Pikaard, C. S. (2008) Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes, Cell, 135, 635-648, https://doi.org/10.1016/j.cell.2008.09.035.
  38. El-Shami, M., Pontier, D., Lahmy, S., Braun, L., Picart, C., Vega, D., Hakimi, M. A., Jacobsen, S. E., Cooke, R., and Lagrange, T. (2007) Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE-binding platforms in RNAi-related components, Genes Dev., 21, 2539-2544, https://doi.org/10.1101/gad.451207.
  39. Köllen, K., Dietz, L., Bies-Etheve, N., Lagrange, T., Grasser, M., and Grasser, K. D. (2015) The zinc-finger protein SPT4 interacts with SPT5L/KTF1 and modulates transcriptional silencing in Arabidopsis, FEBS Lett., 589, 3254-3257, https://doi.org/10.1016/j.febslet.2015.09.017.
  40. Rowley, M. J., Avrutsky, M. I., Sifuentes, C. J., Pereira, L., and Wierzbicki, A. T. (2011) Independent chromatin binding of ARGONAUTE4 and SPT5L/KTF1 mediates transcriptional gene silencing, PLoS Genet., 7, e1002120, https://doi.org/10.1371/journal.pgen.1002120.
  41. Kanno, T., Mette, M. F., Kreil, D. P., Aufsatz, W., Matzke, M., and Matzke, A. J. (2004) Involvement of putative SNF2 chromatin remodeling protein DRD1 in RNA-directed DNA methylation, Curr. Biol., 14, 801-805, https://doi.org/10.1016/j.cub.2004.04.037.
  42. Kanno, T., Bucher, E., Daxinger, L., Huettel, B., Böhmdorfer, G., Gregor, W., Kreil, D. P., Matzke, M., and Matzke, A. J. (2008) A structural-maintenance-of-chromosomes hinge domain-containing protein is required for RNA-directed DNA methylation, Nat. Genet., 40, 670-675, https://doi.org/10.1038/ng.119.
  43. Law, J. A., Ausin, I., Johnson, L. M., Vashisht, A. A., Zhu, J. K., Wohlschlegel, J. A., and Jacobsen, S. E. (2010) A protein complex required for polymerase V transcripts and RNA-directed DNA methylation in Arabidopsis, Curr. Biol., 20, 951-956, https://doi.org/10.1016/j.cub.2010.03.062.
  44. Zhong, X., Hale, C. J., Law, J. A., Johnson, L. M., Feng, S., Tu, A., and Jacobsen, S. E. (2012) DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons, Nat. Struct. Mol. Biol., 19, 870-875, https://doi.org/10.1038/nsmb.2354.
  45. Kuhlmann, M., and Mette, M. F. (2012) Developmentally non-redundant SET domain proteins SUVH2 and SUVH9 are required for transcriptional gene silencing in Arabidopsis thaliana, Plant Mol. Biol., 79, 623-633, https://doi.org/10.1007/s11103-012-9934-x.
  46. Johnson, L. M., Law, J. A., Khattar, A., Henderson, I. R., and Jacobsen, S. E. (2008) SRA-domain proteins required for DRM2-mediated de novo DNA methylation, PLoS Genet., 4, e1000280, https://doi.org/10.1371/journal.pgen.1000280.
  47. Ausin, I., Greenberg, M. V., Simanshu, D. K., Hale, C. J., Vashisht, A. A., Simon, S. A., Lee, T. F., Feng, S., Española, S. D., Meyers, B. C., Wohlschlegel, J. A., Patel, D. J., and Jacobsen, S. E. (2012) INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis, Proc. Natl. Acad. Sci. USA, 109, 8374-8381, https://doi.org/10.1073/pnas.1206638109.
  48. Ausin, I., Mockler, T. C., Chory, J., and Jacobsen, S. E. (2009) IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis thaliana, Nat. Struct. Mol. Biol., 16, 1325-1327, https://doi.org/10.1038/nsmb.1690.
  49. Xie, M., Ren, G., Costa-Nunes, P., Pontes, O., and Yu, B. (2012) A subgroup of SGS3-like proteins act redundantly in RNA-directed DNA methylation, Nucleic Acids Res., 40, 4422-4431, https://doi.org/10.1093/nar/gks034.
  50. Zhu, Y., Rowley, M. J., Böhmdorfer, G., and Wierzbicki, A. T. (2013) A SWI/SNF chromatin-remodeling complex acts in noncoding RNA-mediated transcriptional silencing, Mol. Cell, 49, 298-309, https://doi.org/10.1016/j.molcel.2012.11.011.
  51. Sigman, M. J., and Slotkin, R. K. (2016) The first rule of plant transposable element silencing: location, location, location, Plant Cell, 28, 304-313, https://doi.org/10.1105/tpc.15.00869.
  52. English, J. J., and Jones, J. D. (1998) Epigenetic instability and trans-silencing interactions associated with an SPT::Ac T-DNA locus in tobacco, Genetics, 148, 457-469, https://doi.org/10.1093/genetics/148.1.457.
  53. Gouil, Q., and Baulcombe, D. C. (2018) Paramutation-like features of multiple natural epialleles in tomato, BMC Genomics, 19, 203, https://doi.org/10.1186/s12864-018-4590-4.
  54. Chopra, S., Athma, P., Li, X. G., and Peterson, T. (1998) A maize Myb homolog is encoded by a multicopy gene complex, Mol. Gen. Genet., 260, 372-380, https://doi.org/10.1007/s004380050906.
  55. Springer, N. M., and McGinnis, K. M. (2015) Paramutation in evolution, population genetics and breeding, Semin. Cell Dev. Biol., 44, 33-38, https://doi.org/10.1016/j.semcdb.2015.08.010.
  56. Coe, E. H. (1959) A regular and continuing conversion-type phenomenon at the B locus in maize, Proc. Natl. Acad. Sci. USA, 45, 828-832, https://doi.org/10.1073/pnas.45.6.828.
  57. Haring, M., Bader, R., Louwers, M., Schwabe, A., van Driel, R., and Stam, M. (2010) The role of DNA methylation, nucleosome occupancy and histone modifications in paramutation, Plant J., 63, 366-378, https://doi.org/10.1111/j.1365-313X.2010.04245.x.
  58. Hövel, I., Pearson, N. A., and Stam, M. (2015) Cis-acting determinants of paramutation, Semin. Cell Dev. Biol., 44, 22-32, https://doi.org/10.1016/j.semcdb.2015.08.012.
  59. Walker, E. L., and Panavas, T. (2001) Structural features and methylation patterns associated with paramutation at the r1 locus of Zea mays, Genetics, 159, 1201-1215, https://doi.org/10.1093/genetics/159.3.1201.
  60. Belele, C. L., Sidorenko, L., Stam, M., Bader, R., Arteaga-Vazquez, M. A., and Chandler, V. L. (2013) Specific tandem repeats are sufficient for paramutation-induced trans-generational silencing, PLoS Genetics, 9, e1003773, https://doi.org/10.1371/journal.pgen.1003773.
  61. Stam, M., Belele, C., Dorweiler, J. E., and Chandler, V. L. (2002) Differential chromatin structure within a tandem array 100 kb upstream of the maize b1 locus is associated with paramutation, Genes Dev., 16, 1906-1918, https://doi.org/10.1101/gad.1006702.
  62. Stam, M., Belele, C., Ramakrishna, W., Dorweiler, J. E., Bennetzen, J. L., and Chandler, V. L. (2002) The regulatory regions required for B′ paramutation and expression are located far upstream of the maize b1 transcribed sequences, Genetics, 162, 917-930, https://doi.org/10.1093/genetics/162.2.917.
  63. Louwers, M., Bader, R., Haring, M., van Driel, R., de Laat, W., and Stam, M. (2009) Tissue- and expression level-specific chromatin looping at maize b1 epialleles, Plant Cell, 21, 832-842, https://doi.org/10.1105/tpc.108.064329.
  64. Dorweiler, J. E., Carey, C. C., Kubo, K. M., Hollick, J. B., Kermicle, J. L., and Chandler, V. L. (2000) Mediator of paramutation1 is required for establishment and maintenance of paramutation at multiple maize loci, Plant Cell, 12, 2101-2118, https://doi.org/10.1105/tpc.12.11.2101.
  65. Erhard, K. F., Jr., Stonaker, J. L., Parkinson, S. E., Lim, J. P., Hale, C. J., and Hollick, J. B. (2009) RNA polymerase IV functions in paramutation in Zea mays, Science, 323, 1201-1205, https://doi.org/10.1126/science.1164508.
  66. Hale, C. J., Erhard, K. F., Jr., Lisch, D., and Hollick, J. B. (2009) Production and processing of siRNA precursor transcripts from the highly repetitive maize genome, PLoS Genet., 5, e1000598, https://doi.org/10.1371/journal.pgen.1000598.
  67. Hollick, J. B., and Chandler, V. L. (2001) Genetic factors required to maintain repression of a paramutagenic maize pl1 allele, Genetics, 157, 369-378, https://doi.org/10.1093/genetics/157.1.369.
  68. Nobuta, K., Lu, C., Shrivastava, R., Pillay, M., De Paoli, E., Accerbi, M., Arteaga-Vazquez, M., Sidorenko, L., Jeong, D. H., Yen, Y., Green, P. J., Chandler, V. L., and Meyers, B. C. (2008) Distinct size distribution of endogeneous siRNAs in maize: Evidence from deep sequencing in the mop1-1 mutant, Proc. Natl. Acad. Sci. USA, 105, 14958-14963, https://doi.org/10.1073/pnas.0808066105.
  69. Sidorenko, L., Dorweiler, J. E., Cigan, A. M., Arteaga-Vazquez, M., Vyas, M., Kermicle, J., Jurcin, D., Brzeski, J., Cai, Y., and Chandler, V. L. (2009) A dominant mutation in mediator of paramutation2, one of three second-largest subunits of a plant-specific RNA polymerase, disrupts multiple siRNA silencing processes, PLoS Genet., 5, e1000725, https://doi.org/10.1371/journal.pgen.1000725.
  70. Sekhon, R. S., Wang, P. H., Sidorenko, L., Chandler, V. L., and Chopra, S. (2012) Maize Unstable factor for orange1 is required for maintaining silencing associated with paramutation at the pericarp color1 and booster1 loci, PLoS Genet., 8, e1002980, https://doi.org/10.1371/journal.pgen.1002980.
  71. Sloan, A. E., Sidorenko, L., and McGinnis, K. M. (2014) Diverse gene-silencing mechanisms with distinct requirements for RNA polymerase subunits in Zea mays, Genetics, 198, 1031-1042, https://doi.org/10.1534/genetics.114.168518.
  72. El-Sappah, A. H., Yan, K., Huang, Q., Islam, M. M., Li, Q., Wang, Y., Khan, M. S., Zhao, X., Mir, R. R., Li, J., El-Tarabily, K. A., and Abbas, M. (2021) Comprehensive mechanism of gene silencing and its role in plant growth and development, Front. Plant Sci., 12, 705249, https://doi.org/10.3389/fpls.2021.705249.
  73. Arteaga-Vazquez, M., Sidorenko, L., Rabanal, F. A., Shrivistava, R., Nobuta, K., Green, P. J., Meyers, B. C., and Chandler, V. L. (2010) RNA-mediated trans-communication can establish paramutation at the b1 locus in maize, Proc. Natl. Acad. Sci. USA, 107, 12986-12991, https://doi.org/10.1073/pnas.1007972107.
  74. Haag, J. R., Ream, T. S., Marasco, M., Nicora, C. D., Norbeck, A. D., Pasa-Tolic, L., and Pikaard, C. S. (2012) In vitro transcription activities of Pol IV, Pol V, and RDR2 reveal coupling of Pol IV and RDR2 for dsRNA synthesis in plant RNA silencing, Mol. Cell, 48, 811-818, https://doi.org/10.1016/j.molcel.2012.09.027.
  75. Brzeska, K., Brzeski, J., Smith, J., and Chandler, V. L. (2010) Transgenic expression of CBBP, a CXC domain protein, establishes paramutation in maize, Proc. Natl. Acad. Sci. USA, 107, 5516-5521, https://doi.org/10.1073/pnas.1001576107.
  76. Creasey, K. M., and Martienssen, R. A. (2010) Germline reprogramming of heterochromatin in plants, Cold Spring Harbor Symp. Quantitat. Biol., 75, 269-274, https://doi.org/10.1101/sqb.2010.75.064.
  77. Slotkin, R. K., Vaughn, M., Borges, F., Tanurdzić, M., Becker, J. D., Feijó, J. A., and Martienssen, R. A. (2009) Epigenetic reprogramming and small RNA silencing of transposable elements in pollen, Cell, 136, 461-472, https://doi.org/10.1016/j.cell.2008.12.038.
  78. Olmedo-Monfil, V., Durán-Figueroa, N., Arteaga-Vázquez, M., Demesa-Arévalo, E., Autran, D., Grimanelli, D., Slotkin, R. K., Martienssen, R. A., and Vielle-Calzada, J. P. (2010) Control of female gamete formation by a small RNA pathway in Arabidopsis, Nature, 464, 628-632, https://doi.org/10.1038/nature08828.
  79. Hsieh, T. F., Ibarra, C. A., Silva, P., Zemach, A., Eshed-Williams, L., Fischer, R. L., and Zilberman, D. (2009) Genome-wide demethylation of Arabidopsis endosperm, Science, 324, 1451-1454, https://doi.org/10.1126/science.1172417.
  80. Mosher, R. A., Melnyk, C. W., Kelly, K. A., Dunn, R. M., Studholme, D. J., and Baulcombe, D. C. (2009) Uniparental expression of PolIV-dependent siRNAs in developing endosperm of Arabidopsis, Nature, 460, 283-286, https://doi.org/10.1038/nature08084.
  81. Siomi, H., and Siomi, M. C. (2011) Stress signaling etches heritable marks on chromatin, Cell, 145, 1005-1007, https://doi.org/10.1016/j.cell.2011.06.009.
  82. Höck, J., and Meister, G. (2008) The Argonaute protein family, Genome Biol., 9, 210, https://doi.org/10.1186/gb-2008-9-2-210.
  83. Brennecke, J., Aravin, A. A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., and Hannon, G. J. (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila, Cell, 128, 1089-1103, https://doi.org/10.1016/j.cell.2007.01.043.
  84. Czech, B., Munafò, M., Ciabrelli, F., Eastwood, E. L., Fabry, M. H., Kneuss, E., and Hannon, G. J. (2018) piRNA-guided genome defense: from biogenesis to silencing, Annu. Rev. Genet., 52, 131-157, https://doi.org/10.1146/annurev-genet-120417-031441.
  85. Vagin, V. V., Sigova, A., Li, C., Seitz, H., Gvozdev, V., and Zamore, P. D. (2006) A distinct small RNA pathway silences selfish genetic elements in the germline, Science, 313, 320-324, https://doi.org/10.1126/science.1129333.
  86. Roche, S. E., and Rio, D. C. (1998) Trans-silencing by P elements inserted in subtelomeric heterochromatin involves the Drosophila Polycomb group gene, Enhancer of zeste, Genetics, 149, 1839-1855, https://doi.org/10.1093/genetics/149.4.1839.
  87. Josse, T., Teysset, L., Todeschini, A. L., Sidor, C. M., Anxolabéhère, D., and Ronsseray, S. (2007) Telomeric trans-silencing: an epigenetic repression combining RNA silencing and heterochromatin formation, PLoS Genet., 3, 1633-1643, https://doi.org/10.1371/journal.pgen.0030158.
  88. Ronsseray, S., Boivin, A., and Anxolabéhère, D. (2001) P-Element repression in Drosophila melanogaster by variegating clusters of P-lacZ-white transgenes, Genetics, 159, 1631-1642, https://doi.org/10.1093/genetics/159.4.1631.
  89. Kidwell, M. G., Kidwell, J. F., and Sved, J. A. (1977) Hybrid dysgenesis in Drosophila melanogaster: A syndrome of aberrant traits including mutation, sterility and male recombination, Genetics, 86, 813-833, https://doi.org/10.1093/genetics/86.4.813.
  90. De Vanssay, A., Bougé, A. L., Boivin, A., Hermant, C., Teysset, L., Delmarre, V., Antoniewski, C., and Ronsseray, S. (2012) Paramutation in Drosophila linked to emergence of a piRNA-producing locus, Nature, 490, 112-115, https://doi.org/10.1038/nature11416.
  91. De Vanssay, A., Bougé, A. L., Boivin, A., Hermant, C., Teysset, L., Delmarre, V., Antoniewski, C., and Ronsseray, S. (2013) piRNAs and epigenetic conversion in Drosophila, Fly, 7, 237-241, https://doi.org/10.4161/fly.26522.
  92. Hermant, C., Boivin, A., Teysset, L., Delmarre, V., Asif-Laidin, A., van den Beek, M., Antoniewski, C., and Ronsseray, S. (2015) Paramutation in Drosophila requires both nuclear and cytoplasmic actors of the piRNA pathway and induces cis-spreading of piRNA production, Genetics, 201, 1381-1396, https://doi.org/10.1534/genetics.115.180307.
  93. Sienski, G., Dönertas, D., and Brennecke, J. (2012) Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression, Cell, 151, 964-980, https://doi.org/10.1016/j.cell.2012.10.040.
  94. Le Thomas, A., Rogers, A. K., Webster, A., Marinov, G. K., Liao, S. E., Perkins, E. M., Hur, J. K., Aravin, A. A., and Tóth, K. F. (2013) Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state, Genes Dev., 27, 390-399, https://doi.org/10.1101/gad.209841.112.
  95. Le Thomas, A., Marinov, G. K., and Aravin, A. A. (2014) A transgenerational process defines piRNA biogenesis in Drosophila virilis, Cell Rep., 8, 1617-1623, https://doi.org/10.1016/j.celrep.2014.08.013.
  96. Le Thomas, A., Stuwe, E., Li, S., Du, J., Marinov, G., Rozhkov, N., Chen, Y. C., Luo, Y., Sachidanandam, R., Toth, K. F., Patel, D., and Aravin, A. A. (2014) Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing, Genes Dev., 28, 1667-1680, https://doi.org/10.1101/gad.245514.114.
  97. Mohn, F., Sienski, G., Handler, D., and Brennecke, J. (2014) The rhino-deadlock-cutoff complex licenses noncanonical transcription of dual-strand piRNA clusters in Drosophila, Cell, 157, 1364-1379, https://doi.org/10.1016/j.cell.2014.04.031.
  98. Blumenstiel, J. P., Erwin, A. A., and Hemmer, L. W. (2016) What drives positive selection in the Drosophila piRNA machinery? The genomic autoimmunity hypothesis, Yale J. Biol. Med., 89, 499-512.
  99. Erwin, A. A., Galdos, M. A., Wickersheim, M. L., Harrison, C. C., Marr, K. D., Colicchio, J. M., and Blumenstiel, J. P. (2015) piRNAs are associated with diverse transgenerational effects on gene and transposon expression in a hybrid dysgenic syndrome of D. virilis, PLoS Genet., 11, e1005332, https://doi.org/10.1371/journal.pgen.1005332.
  100. Tsuji, J., Thomson, T., Brown, C., Ghosh, S., Theurkauf, W. E., Weng, Z., and Schwartz, L. M. (2021) Somatic piRNAs and transposons are differentially expressed coincident with skeletal muscle atrophy and programmed cell death, Front. Genet., 12, 775369, https://doi.org/10.3389/fgene.2021.775369.
  101. Rozhkov, N. V., Aravin, A. A., Zelentsova, E. S., Schostak, N. G., Sachidanandam, R., McCombie, W. R., Hannon, G. J., and Evgen’ev, M. B. (2010) Small RNA-based silencing strategies for transposons in the process of invading Drosophila species, RNA, 16, 1634-1645, https://doi.org/10.1261/rna.2217810.
  102. Dorador, A. P., Dalikova, M., Cerbin, S., Stillman, C. M., Zych, M. G., Hawley, R. S., Miller, D. E., Ray, D. A., Funikov, S. Y., Evgen’ev, M. B., and Blumenstiel, J. P. (2022) Paramutation-like epigenetic conversion by piRNA at the telomere of Drosophila virilis, Biology, 11, https://doi.org/10.3390/biology11101480.
  103. Kalmykova, A. I., and Sokolova, O. A. (2023) Retrotransposons and telomeres, Biochemistry (Moscow), 88, 1739-1753, https://doi.org/10.1134/s0006297923110068.
  104. Scarpa, A., and Kofler, R. (2023) The impact of paramutations on the invasion dynamics of transposable elements, Genetics, 225, https://doi.org/10.1093/genetics/iyad181.
  105. Shpiz, S., Ryazansky, S., Olovnikov, I., Abramov, Y., and Kalmykova, A. (2014) Euchromatic transposon insertions trigger production of novel Pi- and endo-siRNAs at the target sites in the drosophila germline, PLoS Genet., 10, e1004138, https://doi.org/10.1371/journal.pgen.1004138.
  106. Ciabrelli, F., Comoglio, F., Fellous, S., Bonev, B., Ninova, M., Szabo, Q., Xuéreb, A., Klopp, C., Aravin, A., Paro, R., Bantignies, F., and Cavalli, G. (2017) Stable polycomb-dependent transgenerational inheritance of chromatin states in Drosophila, Nat. Genet., 49, 876-886, https://doi.org/10.1038/ng.3848.
  107. Steffen, P. A., and Ringrose, L. (2014) What are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory, Nat. Rev. Mol. Cell Biol., 15, 340-356, https://doi.org/10.1038/nrm3789.
  108. Bantignies, F., Grimaud, C., Lavrov, S., Gabut, M., and Cavalli, G. (2003) Inheritance of Polycomb-dependent chromosomal interactions in Drosophila, Genes Dev., 17, 2406-2420, https://doi.org/10.1101/gad.269503.
  109. Ashe, A., Sapetschnig, A., Weick, E. M., Mitchell, J., Bagijn, M. P., Cording, A. C., Doebley, A. L., Goldstein, L. D., Lehrbach, N. J., Le Pen, J., Pintacuda, G., Sakaguchi, A., Sarkies, P., Ahmed, S., and Miska, E. A. (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans, Cell, 150, 88-99, https://doi.org/10.1016/j.cell.2012.06.018.
  110. Bagijn, M. P., Goldstein, L. D., Sapetschnig, A., Weick, E. M., Bouasker, S., Lehrbach, N. J., Simard, M. J., and Miska, E. A. (2012) Function, targets, and evolution of Caenorhabditis elegans piRNAs, Science, 337, 574-578, https://doi.org/10.1126/science.1220952.
  111. Lee, H. C., Gu, W., Shirayama, M., Youngman, E., Conte, D., Jr., and Mello, C. C. (2012) C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts, Cell, 150, 78-87, https://doi.org/10.1016/j.cell.2012.06.016.
  112. Shirayama, M., Seth, M., Lee, H. C., Gu, W., Ishidate, T., Conte, D., Jr., and Mello, C. C. (2012) piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline, Cell, 150, 65-77, https://doi.org/10.1016/j.cell.2012.06.015.
  113. Shukla, A., Yan, J., Pagano, D. J., Dodson, A. E., Fei, Y., Gorham, J., Seidman, J. G., Wickens, M., and Kennedy, S. (2020) poly(UG)-tailed RNAs in genome protection and epigenetic inheritance, Nature, 582, 283-288, https://doi.org/10.1038/s41586-020-2323-8.
  114. Tsai, H. Y., Chen, C. C., Conte, D., Jr., Moresco, J. J., Chaves, D. A., Mitani, S., Yates, J. R., 3rd, Tsai, M. D., and Mello, C. C. (2015) A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi, Cell, 160, 407-419, https://doi.org/10.1016/j.cell.2015.01.010.
  115. Yigit, E., Batista, P. J., Bei, Y., Pang, K. M., Chen, C. C., Tolia, N. H., Joshua-Tor, L., Mitani, S., Simard, M. J., and Mello, C. C. (2006) Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi, Cell, 127, 747-757, https://doi.org/10.1016/j.cell.2006.09.033.
  116. Buckley, B. A., Burkhart, K. B., Gu, S. G., Spracklin, G., Kershner, A., Fritz, H., Kimble, J., Fire, A., and Kennedy, S. (2012) A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality, Nature, 489, 447-451, https://doi.org/10.1038/nature11352.
  117. Mao, H., Zhu, C., Zong, D., Weng, C., Yang, X., Huang, H., Liu, D., Feng, X., and Guang, S. (2015) The Nrde pathway mediates small-RNA-directed histone H3 lysine 27 trimethylation in Caenorhabditis elegans, Curr. Biol., 25, 2398-2403, https://doi.org/10.1016/j.cub.2015.07.051.
  118. Schwartz-Orbach, L., Zhang, C., Sidoli, S., Amin, R., Kaur, D., Zhebrun, A., Ni, J., and Gu, S. G. (2020) Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3, eLife, 9, e54309, https://doi.org/10.7554/eLife.54309.
  119. Shen, E. Z., Chen, H., Ozturk, A. R., Tu, S., Shirayama, M., Tang, W., Ding, Y. H., Dai, S. Y., Weng, Z., and Mello, C. C. (2018) Identification of piRNA binding sites reveals the Argonaute regulatory landscape of the C. elegans germline, Cell, 172, 937-951.e918, https://doi.org/10.1016/j.cell.2018.02.002.
  120. Zhang, D., Tu, S., Stubna, M., Wu, W. S., Huang, W. C., Weng, Z., and Lee, H. C. (2018) The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes, Science, 359, 587-592, https://doi.org/10.1126/science.aao2840.
  121. Seth, M., Shirayama, M., Gu, W., Ishidate, T., Conte, D., Jr., and Mello, C. C. (2013) The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression, Dev. Cell, 27, 656-663, https://doi.org/10.1016/j.devcel.2013.11.014.
  122. Wedeles, C. J., Wu, M. Z., and Claycomb, J. M. (2013) Protection of germline gene expression by the C. elegans Argonaute CSR-1, Dev. Cell, 27, 664-671, https://doi.org/10.1016/j.devcel.2013.11.016.
  123. Singh, M., Cornes, E., Li, B., Quarato, P., Bourdon, L., Dingli, F., Loew, D., Proccacia, S., and Cecere, G. (2021) Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis, Nat. Commun., 12, 3492, https://doi.org/10.1038/s41467-021-23615-w.
  124. Gu, W., Shirayama, M., Conte, D., Jr., Vasale, J., Batista, P. J., Claycomb, J. M., Moresco, J. J., Youngman, E. M., Keys, J., Stoltz, M. J., Chen, C. C., Chaves, D. A., Duan, S., Kasschau, K. D., Fahlgren, N., Yates, J. R., 3rd, Mitani, S., Carrington, J. C., and Mello, C. C. (2009) Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline, Mol. Cell, 36, 231-244, https://doi.org/10.1016/j.molcel.2009.09.020.
  125. Pak, J., and Fire, A. (2007) Distinct populations of primary and secondary effectors during RNAi in C. elegans, Science, 315, 241-244, https://doi.org/10.1126/science.1132839.
  126. Goodwin, E. B., and Ellis, R. E. (2002) Turning clustering loops: sex determination in Caenorhabditis elegans, Curr. Biol., 12, R111-120, https://doi.org/10.1016/s0960-9822(02)00675-9.
  127. Johnson, C. L., and Spence, A. M. (2011) Epigenetic licensing of germline gene expression by maternal RNA in C. elegans, Science, 333, 1311-1314, https://doi.org/10.1126/science.1208178.
  128. Sapetschnig, A., Sarkies, P., Lehrbach, N. J., and Miska, E. A. (2015) Tertiary siRNAs mediate paramutation in C. elegans, PLoS Genet., 11, e1005078, https://doi.org/10.1371/journal.pgen.1005078.
  129. Rassoulzadegan, M., Grandjean, V., Gounon, P., Vincent, S., Gillot, I., and Cuzin, F. (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse, Nature, 441, 469-474, https://doi.org/10.1038/nature04674.
  130. Bernex, F., De Sepulveda, P., Kress, C., Elbaz, C., Delouis, C., and Panthier, J. J. (1996) Spatial and temporal patterns of c-kit-expressing cells in WlacZ/+ and WlacZ/WlacZ mouse embryos, Development, 122, 3023-3033, https://doi.org/10.1242/dev.122.10.3023.
  131. Yuan, S., Oliver, D., Schuster, A., Zheng, H., and Yan, W. (2015) Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice, Sci. Rep., 5, 9266, https://doi.org/10.1038/srep09266.
  132. Nocka, K., Tan, J. C., Chiu, E., Chu, T. Y., Ray, P., Traktman, P., and Besmer, P. (1990) Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W, EMBO J., 9, 1805-1813, https://doi.org/10.1002/j.1460-2075.1990.tb08305.x.
  133. Grandjean, V., Gounon, P., Wagner, N., Martin, L., Wagner, K. D., Bernex, F., Cuzin, F., and Rassoulzadegan, M. (2009) The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth, Development, 136, 3647-3655, https://doi.org/10.1242/dev.041061.
  134. Wagner, K. D., Wagner, N., Ghanbarian, H., Grandjean, V., Gounon, P., Cuzin, F., and Rassoulzadegan, M. (2008) RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse, Dev. Cell, 14, 962-969, https://doi.org/10.1016/j.devcel.2008.03.009.
  135. Kiani, J., Grandjean, V., Liebers, R., Tuorto, F., Ghanbarian, H., Lyko, F., Cuzin, F., and Rassoulzadegan, M. (2013) RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2, PLoS Genet., 9, e1003498, https://doi.org/10.1371/journal.pgen.1003498.
  136. Bartel, D. P. (2018) Metazoan microRNAs, Cell, 173, 20-51, https://doi.org/10.1016/j.cell.2018.03.006.
  137. Truesdell, S. S., Mortensen, R. D., Seo, M., Schroeder, J. C., Lee, J. H., LeTonqueze, O., and Vasudevan, S. (2012) MicroRNA-mediated mRNA translation activation in quiescent cells and oocytes involves recruitment of a nuclear microRNP, Sci. Rep., 2, 842, https://doi.org/10.1038/srep00842.
  138. Vasudevan, S., Tong, Y., and Steitz, J. A. (2007) Switching from repression to activation: microRNAs can up-regulate translation, Science, 318, 1931-1934, https://doi.org/10.1126/science.1149460.
  139. Cuzin, F., Grandjean, V., and Rassoulzadegan, M. (2008) Inherited variation at the epigenetic level: paramutation from the plant to the mouse, Curr. Opin. Genet. Dev., 18, 193-196, https://doi.org/10.1016/j.gde.2007.12.004.
  140. Czene, K., Lichtenstein, P., and Hemminki, K. (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family-cancer database, Int. J. Cancer, 99, 260-266, https://doi.org/10.1002/ijc.10332.
  141. Lesch, B. J., Tothova, Z., Morgan, E. A., Liao, Z., Bronson, R. T., Ebert, B. L., and Page, D. C. (2019) Intergenerational epigenetic inheritance of cancer susceptibility in mammals, eLife, 8, e39380, https://doi.org/10.7554/eLife.39380.
  142. You, J. S., and Jones, P. A. (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell, 22, 9-20, https://doi.org/10.1016/j.ccr.2012.06.008

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Comparison of classical inheritance of traits according to Mendel and with paramutation using the b1 locus in maize as an example. a – Classical segregation of traits in the progeny of first and second generation hybrids in accordance with Mendel’s first and second laws (top); the emergence of the a′ allele as a result of paramutation, which has the “A” phenotype, while the “a” phenotype disappears and is no longer manifested in generations (bottom). Red color – phenotype “A”, blue color – phenotype “a”. b – Interaction of alleles B-I (purple phenotype) and B′ (green phenotype) leads to the formation of the B′* allele and the manifestation of only the “green phenotype” in the first generation (F1) progeny. When F1 plants are further crossed with each other or when backcrossing with a homozygous B-I parent, all offspring will also have a “green phenotype” regardless of the genotype of the parents.

Download (224KB)
Indexing metadata
3. Fig. 2. Canonical RNA-directed DNA methylation pathway (RdDM pathway) in plants. The canonical RdDM pathway begins with transcription of siRNA precursors from genomic loci by Pol IV. NRPD1 is the largest subunit of Pol IV. Pol IV is recruited to genomic loci by the proteins SHH1 and CLSY, which recognize both H3K4me0 (unmethylated lysine) and H3K9me2. Then, the second complementary RNA strand is synthesized on the siRNA precursor template by RdRP, RDR2. Next, the DCL3 protein “cuts” dsRNA into 24-nucleotide siRNAs, which undergo methylation of the protruding 3′-terminal ribonucleotides by the RNA methyltransferase HEN1. In the final step of formation, the siRNA guide strand is loaded into one of the Ago proteins (Ago4, Ago6, or Ago9) and binds to the complementary target RNA. The siRNA-loaded Ago protein interacts with NRPE1, the largest subunit of Pol V, and recruits the SPT5L factor. The Pol V–Ago4–SPT5L complex then recruits the methyltransferase DRM2, which catalyzes de novo DNA methylation, to the genomic locus. The DDR complex, which includes the factors DRD1, DMS3, and RDM1, as well as the proteins SUVH2 and SUVH9, is involved in the recruitment of Pol V to the genomic locus and its methylation. The IDN2–IDP complex, which is bound simultaneously to DNA and transcribed RNA, recruits the ATP-dependent chromatin remodeling complex SWI–SNF to the locus to facilitate DNA methylation

Download (228KB)
Indexing metadata
4. Fig. 3. Comparative structure of different types of alleles of the b1 locus in maize. At a distance of ~100 kb from the start of transcription of the b1 gene, there are 853 bp tandem repeats (marked with red-green circles, where red denotes the 3'-terminal part of the repeat, and green denotes the 5'-terminal part). The efficiency of the paramutagenic effect in the b1 locus depends on the number of repeats and their structure.

Download (128KB)
Indexing metadata
5. Fig. 4. Paramutation in D. melanogaster upon crossing the T-1 and BX2 lines. a – The T-1 and BX2 lines carry transgenic constructs containing 7 tandem repeats of P-lacZ. In the BX2 line, the lacZ reporter gene is expressed (the blue color appears upon incubation of the ovaries in a solution with X-gal). In the T-1 line, the transgene expression is suppressed, therefore the ovaries are not stained. P – parental lines; G – generation; Bal1 and Bal2 – balancer chromosomes. b – Putative mechanism of piRNA-mediated transformation of the BX2 locus into a piRNA cluster during paramutation. PiRNAs originating from the T-1 locus are loaded into the Piwi protein. Piwi–piRNA complexes are then maternally inherited and bind to newly formed transcripts from the BX2 locus and recruit the histone methyltransferase SetDB1/Egg, which methylates H3K9. This constitutes cotranscriptional silencing of the locus. Following epigenetic modification of the locus, the Rhino–Cutoff complex binds to H3K9me3 and initiates piRNA cluster formation. After export from the nucleus to the cytoplasm, piRNA cluster transcripts undergo endonucleotic cleavage by Zuc/MitoPLD. All piRNAs produced by Zuc nuclease activity are characterized by a strong nucleotide preference for uridine at the 5′ end of piRNA molecules. Next, piRNA molecules are loaded into a complex with the Piwi protein, which carries out cotranscriptional silencing of the BX2* locus and is also transmitted to the next generation through the oocyte cytoplasm.

Download (243KB)
Indexing metadata
6. Fig. 5. Biogenesis of short noncoding RNAs and the self-foe recognition mechanism in C. elegans. In germline cells, piRNA gene clusters produce 21U RNAs that are loaded into PRG-1. The 21U RNA–PRG-1 complex initiates the formation of 22G RNAs from mRNAs by an RNA-dependent RNA polymerase, presumably RRF-1. It is proposed that mRNAs entering the cytoplasm from the nucleus are sequentially checked for sequence matching by CSR-1-bound 22G RNAs and PRG-1-bound 21U RNAs and serve as templates for the formation of additional 22G RNAs. Once 22G RNAs are formed on the mRNA template, these siRNAs are loaded into WAGO-9, enter the nucleus, and recognize a complementary transcript, initiating the recruitment of histone methyltransferases. The 22G-RNA–CSR-1 complex prevents the binding of siRNAs loaded into WAGO-9. Short non-coding RNA molecules within PRG-1 or CSR-1 initiate either the suppression of expression of the foreign sequence or provide permission for transcription (licensed gene) of the native mRNA

Download (289KB)
Indexing metadata
7. Fig. 6. An example of cascade paramutation in the nematode C. elegans

Download (285KB)
Indexing metadata
8. Fig. 7. Paramutation at the Kit locus in mice. Crossing pattern demonstrating modification in the wild-type allele and resulting in the “white tail” phenotype.

Download (99KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».