Неравная экспрессия родительских аллелей в плаценте человека

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Неравная экспрессия родительских аллелей играет основополагающую роль в формировании плаценты как многофункционального органа, необходимого для развития и выживания плода. В первую очередь это выражается в феномене импринтинга, когда в клетках плаценты экспрессируется только материнский или отцовский аллель. Плацента использует более широкий спектр механизмов импринтинга, чем эмбрион, – модификации гистонов, подавляющие или, наоборот, активирующие экспрессию рядом расположенных генов; регуляторные последовательности и гены, полученные от ретровирусов или ретротранспозонов; микроРНК, функционирующие как антисмысловые РНК и принимающие участие в транскрипционной и посттранскрипционной регуляции экспрессии генов. Кроме того, в плаценте обнаруживается неполное подавление активности одного из родительских аллелей, приводящее к смещенной импринтированной экспрессии некоторых генов. В настоящем обзоре показана роль неравной экспрессии родительских аллелей в развитии плацентарных структур эмбриона, обсуждены механизмы эпигенетического контроля родительских аллелей, преимущественно экспрессирующихся в плаценте.

Об авторах

Е. А. Саженова

Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наук

Автор, ответственный за переписку.
Email: elena.sazhenova@medgenetics.ru
Россия, 634050, Томск

С. А. Васильев

Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наук

Email: elena.sazhenova@medgenetics.ru
Россия, 634050, Томск

И. Н. Лебедев

Научно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наук

Email: elena.sazhenova@medgenetics.ru
Россия, 634050, Томск

Список литературы

  1. Gui B., Slone J., Huang T. Perspective: Is random monoallelic expression a contributor to phenotypic variability of autosomal dominant disorders? // Front. Genet. 2017. V. 29(8). P. e191. https://doi.org/10.3389/fgene.2017.00191
  2. Pilvar D., Reiman M., Pilvar A., Laan M. Parent-of-origin-specific allelic expression in the human placenta is limited to established imprinted loci and it is stably maintained across pregnancy // Clin. Epigenet. 2019. V. 11. P. e94. https://doi.org/10.1186/s13148-019-0692-3
  3. Tucci V., Isles A.R., Kelsey G. et al. Genomic imprinting and physiological processes in mammals // Cell. 2019. V. 176. P. 952–965. https://doi.org/10.1016/j.cell.2019.01.043
  4. Bogutz A.B., Brind A.J., Kobayashi H. et al. Evolution of imprinting via lineage-specific insertion of retroviral promoters // Nat. Commun. 2019. V. 10. P. e5674. https://doi.org/10.1038/s41467-019-13662-9
  5. Raas M.W., Zijlmans D.W., Vermeulen M. et al. There is another: H3K27me3-mediated genomic imprinting // Trends Genet. 2022. V. 38(1). P. 82–96. https://doi.org/10.1016/j.tig.2021.06.017
  6. Cierna Z., Varga I., Danihel L.J. et al. Intermediate trophoblast-A distinctive, unique and often unrecognized population of trophoblastic cells // Ann. Anat. 2016. V. 204. P. 45–50. https://doi.org/10.1016/j.aanat.2015.10.003
  7. Norwitz E.R. Defective implantation and placentation: Laying the blueprint for pregnancy complications // Reprod. Biomed. Online. 2006. V. 13(4). P. 591–599. https://doi.org/10.1016/s1472-6483(10)60649-9
  8. Thamban T., Agarwaal V., Khosla S. Role of genomic imprinting in mammalian development // J. Biosci. 2020. V. 45. P. e20.
  9. Varrault A., Dantec C., Le Digarcher A. et al. Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network // Nucl. Acids Res. 2017. V. 45(18). P. 10466–10480. https://doi.org/10.1093/nar/gkx672
  10. Hanna C.W. Placental imprinting: Emerging mechanisms and functions // PLoS Genet. 2020. V. 16(4). P. e1008709. https://doi.org/10.1371/journal.pgen.1008709
  11. Starks R.R., Kaur H., Tuteja G. Mapping cis-regulatory elements in the midgestation mouse placenta // Sci. Rep. 2021. V. 11. P. e22331. https://doi.org/10.1038/s41598-021-01664-x
  12. Woods L., Perez-Garcia V., Hemberger M. Regulation of placental development and its impact on fetal growth-new insights from mouse models // Front. Endocrinol. (Lausanne). 2018. V. 9. P. e570. https://doi.org/10.3389/fendo.2018.00570
  13. Miri K., Latham K., Panning B. et al. The imprinted polycomb group gene Sfmbt2 is required for trophoblast maintenance and placenta development // Development. 2013. V. 140. P. 4480–4489. https://doi.org/10.1242/dev.096511
  14. Tang P., Miri K., Varmuza S. Unique trophoblast chromatin environment mediated by the PcG protein SFMBT2 // Biol. Open. 2019. V. 8(8). P. e043638. https://doi.org/10.1242/bio.043638
  15. Andergassen D., Dotter C.P., Wenzel D. et al. Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression // Elife. 2017. V. 6. P. e25125. https://doi.org/10.7554/eLife.25125
  16. Schertzer M.D., Braceros K.C., Starmer J. et al. lncRNA‑induced spread of Polycomb controlled by genome architecture, RNA abundance, and CpG island DNA // Mol. Cell. 2019. V. 75(3). P. 523–537. https://doi.org/10.1016/j.molcel.2019.05.028
  17. Bartel D.P. Metazoan MicroRNAs // Cell. 2018. V. 173. P. 20–51. https://doi.org/10.1016/j.cell.2018.03.006
  18. Hayder H., O’Brien J., Nadeem U., Peng C. Micro-RNAs: Crucial regulators of placental development // Reproduction. 2018. V. 155(6). P. R259–R271. https://doi.org/10.1530/REP-17-0603
  19. Malnou E.C., Umlauf D., Mouysset M., Cavaille J. Imprinted microRNA gene clusters in the evolution, development, and functions of mammalian placenta // Front. Genet. 2019. V. 9. P. e706. https://doi.org/10.3389/fgene.2018.00706
  20. Inno R., Kikas T., Lillepea K., Laan M. Coordinated expressional landscape of the human placental miRNome and transcriptome // Front. Cell Dev. Biol. 2021. V. 9. P. e697947. https://doi.org/10.3389/fcell.2021.697947
  21. Kaneko-Ishino T., Ishino F. Retrotransposon silencing by DNA methylation contributed to the evolution of placentation and genomic imprinting in mammals // Dev. Growth Differ. 2010. V. 52(6). P. 533–543. https://doi.org/10.1111/j.1440-169X.2010.01194.x
  22. Ito M., Sferruzzi-Perri A.N., Edwards C.A. et al. A trans-homologue interaction between reciprocally imprinted miR-127 and Rtl1 regulates placenta development // Development. 2015. V. 142(14). P. 2425–2430. https://doi.org/10.1242/dev.121996
  23. Bentwich I. Prediction and validation of microRNAs and their targets // FEBS Lett. 2005. V. 579(26). P. 5904–5910. https://doi.org/10.1016/j.febslet.2005.09.040
  24. Haig D., Mainieri A. The evolution of imprinted microRNAs and their RNA targets // Genes (Basel). 2020. V. 11(9). P. e1038. https://doi.org/10.3390/genes11091038
  25. Noguer-Dance M., Abu-Amero S., Al-Khtib M. et al. The primate-specific microRNA gene cluster (C19MC) is imprinted in the placenta // Hum. Mol. Genet. 2010. V. 19(18). P. 3566–3582. https://doi.org/10.1093/hmg/ddq272
  26. Gottlieb A., Flor I., Nimzyk R. et al. The expression of miRNA encoded by C19MC and miR-371-3 strongly varies among individual placentas but does not differ between spontaneous and induced abortions // Protoplasma. 2021. V. 258(1). P. 209–218. https://doi.org/10.1007/s00709-020-01548
  27. Gu Y., Sun J., Groome L.J., Wang Y. Differential miRNA expression profiles between the first and third trimester human placentas // Am. J. Physiol. Endocrinol. Metab. 2013. V. 304(8). P. 836–843. https://doi.org/10.1152/ajpendo.00660.2012
  28. Munjas J., Sopic M., Stefanovic A. et al. Non-coding RNAs in preeclampsia-molecular mechanisms and diagnostic potential // Int. J. Mol. Sci. 2021. V. 22(19). P. e10652. https://doi.org/10.3390/ijms221910652
  29. Delorme-Axford E., Donker R.B., Mouillet J.F. et al. Human placental trophoblasts confer viral resistance to recipient cells // Proc. Natl Acad. Sci. USA. 2013. V. 110. P. 12048–12053. https://doi.org/10.1073/pnas.1304718110
  30. Ishida Y., Zhao D., Ohkuchi A. et al. Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy // Int. J. Mol. Med. 2015. V. 35. P. 1511–1524. https://doi.org/10.3892/ijmm.2015.2157
  31. Inoue K., Hirose M., Inoue H. et al. The rodent-specific microRNA cluster within the Sfmbt2 gene is imprinted and essential for placental development // Cell Rep. 2017. V. 19. P. 949–956. https://doi.org/10.1016/j.celrep.2017.04.018
  32. Farhadova S., Gomez-Velazquez M., Feil R. Stability and lability of parental methylation imprints in development and disease // Genes (Basel). 2019. V. 10(12). P. e999. https://doi.org/10.3390/genes10120999
  33. Zeng Y., Chen T. DNA methylation reprogramming during mammalian development // Genes (Basel). 2019. V. 10(4). P. e257. https://doi.org/10.3390/genes10040257
  34. Huang Y., Liu H., Du H. et al. Developmental features of DNA methylation in CpG islands of human gametes and preimplantation embryos // Exp. Ther. Med. 2019. V. 17(6). P. 4447–4456. https://doi.org/10.3892/etm.2019.7523
  35. Takahashi N., Coluccio A., Thorball C.W. et al. ZNF445 is a primary regulator of genomic imprinting // Genes Dev. 2019. V. 33. P. 49–54. https://doi.org/10.1101/gad.320069.118
  36. Decato B.E., Lopez-Tello J., Sferruzzi-Perri A.N. et al. DNA methylation divergence and tissue specialization in the developing mouse placenta // Mol. Biol. Evol. 2017. V. 34. P. 1702–1712. https://doi.org/10.1093/molbev/msx112
  37. Duffie R., Ajjan S., Greenberg M.V. et al. The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals // Genes Dev. 2014. V. 28. P. 463–478. https://doi.org/10.1101/gad.232058.113
  38. Chen Z., Djekidel M.N., Zhang Y. Distinct dynamics and functions of H2AK119ub1 and H3K27me3 in mouse preimplantation embryos // Nat. Genet. 2021. V. 53(4). P. 551–563. https://doi.org/10.1038/s41588-021-00821-2
  39. Jambhekar A., Dhall A., Shi Y. Roles and regulation of histone methylation in animal development // Nat. Rev. Mol. Cell Biol. 2019. V. 20(10). P. 625–641. https://doi.org/10.1038/s41580-019-0151-1
  40. Healy E., Mucha M., Glancy E. et al. PRC2.1 and PRC2.2 synergize to coordinate H3K27 trimethylation // Mol. Cell. 2019. V. 76(3). P. 437–452. https://doi.org/10.1016/j.molcel.2019.08.012
  41. Cheutin T., Cavalli G. The multiscale effects of polycomb mechanisms on 3D chromatin folding // Crit. Rev. Biochem. Mol. Biol. 2019. V. 54(5). P. 399–417. https://doi.org/10.1080/10409238.2019.1679082
  42. Yang P., Wang Y., Macfarlan T.S. The role of KRAB-ZFPs in transposable element repression and mammalian evolution // Trends Genet. 2017. V. 33(11). P. 871–881. https://doi.org/10.1016/j.tig.2017.08.006
  43. Xu Q., Xie W. Epigenome in early mammalian development: inheritance, reprogramming and establishment // Trends Cell Biol. 2018. V. 28. P. 237–253.
  44. Prokopuk L., Stringer J.M., White C.R. et al. Loss of maternal EED results in postnatal overgrowth // Clin. Epigenetics. 2018. V. 10(1) P. e95. https://doi.org/10.1186/s13148-018-0526-8
  45. Hanna C.W., Gavin K. Features and mechanisms of canonical and noncanonical genomic imprinting // Genes Dev. 2021. V. 35(11–12). P. 821–834. https://doi.org/10.1101/gad.348422.121
  46. Hanna C.W. Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues // Genome Biol. 2019. V. 20. P. e225. https://doi.org/10.1186/s13059-019-1833-x
  47. Chen Z., Yin Q., Inoue A. et al. Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells // Sci. Adv. 2019. V. 5(12). P. e7246. https://doi.org/10.1126/sciadv.aay7246
  48. Zhang W., Chen Z., Yin Q. et al. Maternal-biased H3K27me3 correlates with paternal-specific gene expression in the human morula // Genes Dev. 2019. V. 33(7–8). P. 382–387. https://doi.org/10.1101/gad.323105.118
  49. Enriquez-Gasca R., Gould P.A., Rowe H.M. Host gene regulation by transposable elements: the new, the old and the ugly // Viruses. 2020. V. 12(10). P. e1089. https://doi.org/10.3390/v12101089
  50. Senft A.D., Macfarlan T.S. Transposable elements shape the evolution of mammalian development // Nat. Rev. Genet. 2021. V. 22(11). P. 691–711. https://doi.org/10.1038/s41576-021-00385-1
  51. Zhang X., Muglia L.J. Baby’s best Foe-riend: Endogenous retroviruses and the evolution of eutherian reproduction // Placenta. 2021. V. 15(113). P. 1–7. https://doi.org/10.1016/j.placenta.2021.02.011
  52. Schust D.J., Bonney E.A., Sugimoto J. et al. The immunology of syncytialized trophoblast // Int. J. Mol. Sci. 2021. V. 2(4). P. e1767. https://doi.org/10.3390/ijms22041767
  53. Sugimoto J., Sugimoto M., Bernstein H. et al. A novel human endogenous retroviral protein inhibits cell-cell fusion // Sci. Rep. 2013. V. 3. P. e1462. https://doi.org/10.1038/srep01462
  54. Roberts R.M., Ezashi T., Schulz L.C. et al. Syncytins expressed in human placental trophoblast // Placenta. 2021. V. 113. P. 8–14. https://doi.org/10.1016/j.placenta.2021.01.006
  55. Каталог импринтированных генов. http://igc.otago.ac.nz.
  56. Roberts R.M., Green J.A., Schulz L.C. The evolution of the placenta // Reproduction. 2016. V. 152. P. 179–189. https://doi.org/10.1530/REP-16-0325
  57. Henke C., Strissel P.L., Schubert M.T. Selective expression of sense and antisense transcripts of the sushi-ichi-related retrotransposon-derived family during mouse placentogenesis // Retrovirology. 2015. V. 12. P. e9. https://doi.org/10.1186/s12977-015-0138-8
  58. Miao J., Zhu Y., Xu L. et al. MiR‑181b‑5Pinhibits trophoblast cell migration and invasion through targeting S1PR1 in multiple abnormal trophoblast invasion‑related events // Mol. Med. Rep. 2020. V. 22(5). P. 4442–4451. https://doi.org/10.3892/mmr.2020.11515
  59. Barlow D.P. Methylation and imprinting: From host defense to gene regulation? // Science. 1993. V. 260. P. 309–310. https://doi.org/10.1126/science.8469984
  60. Ondicova M., Oakey R.J., Walsh C.P. Is imprinting the result of “friendly fire” by the host defense system? // PLoS Genet. 2020. V. 16. P. e1008599. https://doi.org/10.1126/science.8469984
  61. Jahner D., Stuhlmann H., Stewart C.L. et al. De novo methylation and expression of retroviral genomes during mouse embryogenesis // Nature. 1982. V. 298. P. 623–628. https://doi.org/10.1038/298623a0
  62. Chaillet J., Vogt T., Beier D., Leder P. Parental-specific methylation of an imprinted transgene is established during gametogenesis and progressively changes during embryogenesis // Cell. 1991. V. 66. P. 77–83. https://doi.org/10.1016/0092-8674(91)90140-t
  63. Walter J., Hutter B., Khare T., Paulsen M. Repetitive elements in imprinted genes // Cytogenet. Genome Res. 2006. V. 113. P. 109–115. https://doi.org/10.1159/000090821
  64. Cowley M., de Burca A., McCole R.B. et al. Short Interspersed Element (SINE) depletion and Long Interspersed Element (LINE) abundance are not features universally required for imprinting // PLoS One. 2011. V. 6. P. e18953. https://doi.org/10.1371/journal.pone.0018953
  65. Wood A.J., Bourc’his D., Bestor T.H., Oakey R.J. Allele-specific demethylation at an imprinted mammalian promoter // Nucl. Acids Res. 2007. V. 35. P. 7031–7039. https://doi.org/10.1093/nar/gkm742
  66. Wood A.J., Roberts R.G., Monk D. et al. A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation // PLoS Genet. 2007. V. 3. P. e20. https://doi.org/10.1371/journal.pgen.0030020
  67. Youngson N.A., Kocialkowski S., Peel N., Ferguson-Smith A.C. A small family of sushi-class retrotransposon-derived genes in mammals and their relation to genomic imprinting // J. Mol. Evol. 2005. V. 61. P. 481–490. https://doi.org/10.1007/s00239-004-0332-0
  68. Cowley M., Oakey R.J. Retrotransposition and genomic imprinting // Brief. Funct. Genomics. 2010. V. 9. P. 340–346. https://doi.org/10.1093/bfgp/elq015
  69. Thomas J.H., Schneider S. Coevolution of retroelements and tandem zinc finger genes // Genome Res. 2011. V. 21. P. 1800–1812. https://doi.org/10.1101/gr.121749.111
  70. Yang P., Wang Y., Hoang D. et al. A placental growth factor is silenced in mouse embryos by the zinc finger protein ZFP568 // Science. 2017. V. 356. P. 757–759. https://doi.org/10.1126/science.aah6895
  71. Helleboid P., Heusel M., Duc J. et al. The interactome of KRAB zinc finger proteins reveals the evolutionary history of their functional diversification // EMBO J. 2019. V. 38. P. e101220. https://doi.org/10.15252/embj.2018101220
  72. Jacobs F.M., Greenberg D., Nguyen N. et al. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons // Nature. 2014. V. 516. P. 242–245.
  73. Rowe H.M., Friedli M., Offner S. et al. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET // Development. 2013. V. 140. P. 519–529. https://doi.org/10.1242/dev.087585
  74. Imbeault M., Helleboid P.Y., Trono D. KRAB zinc-finger proteins contribute to the evolution of gene regulatory networks // Nature. 2017. V. 543. P. 550–554. https://doi.org/10.1038/nature21683
  75. Strogantsev R., Krueger F., Yamazawa K. et al. Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression // Genome Biol. 2015. V. 16. P. e112. https://doi.org/10.1186/s13059-015-0672-7
  76. Moore T., Haig D. Genomic imprinting in mammalian development: A parental tug-of-war // TIG. 1991. V. 7. P. 45–49. https://doi.org/10.1016/0168-9525(91)90230-N
  77. Quenneville S., Verde G., Corsinotti A. 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. V. 44. P. 361–372. https://doi.org/10.1016/j.molcel.2011.08.032
  78. Li X., Ito M., Zhou F. et al. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints // Dev. Cell. 2008. V. 15. P. 547–557. https://doi.org/10.1016/j.devcel.2008.08.014
  79. Criscione S.W., Theodosakis N., Micevic G. et al. Genome-wide characterization of human L1 antisense promoter-driven transcripts // BMC Genomics. 2016. V. 17. P. e463. https://doi.org/10.1186/s12864-016-2800-5
  80. Castro-Diaz N., Ecco G., Coluccio A. et al. Evolutionally dynamic L1 regulation in embryonic stem cells // Genes Dev. 2014. V. 28(13). P. 397–409. https://doi.org/10.1101/gad.241661.114
  81. Vincenz C., Lovett J.L., Wu W. et al. Loss of imprinting in human placentas is widespread, coordinated, and predicts birth phenotypes // Mol. Biol. Evol. 2020. V. 37(2). P. 429–441. https://doi.org/10.1093/molbev/msz226
  82. Wang X.X., Miller D.C., Harman R. et al. Paternal expressed genes predominate in the placenta // Proc. Natl Acad. Sci. USA. 2013. V. 110. P. 10705–10710. https://doi.org/10.1073/pnas.1308998110
  83. Monteagudo-Sánchez A., Sánchez-Delgado M., Hernandez J.R. et al. Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction // Clin. Epigenetics. 2019. V. 11(1). P. e35. https://doi.org/10.1186/s13148-019-0630-4
  84. Kappil M.A., Green B.B., Armstrong D.A. et al. Placental expression profile of imprinted genes impacts birth weight // Epigenetics. 2015. V. 10(9). P. 842–849. https://doi.org/10.1080/15592294.2015.1073881
  85. Court F., Tayama C., Romanelli V. et al. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment // Genome Res. 2014. V. 24(4). P. 554–569. https://doi.org/10.1101/gr.164913.113
  86. Hanna C.W., Penaherrera M.S., Saadeh H. et al. Pervasive polymorphic imprinted methylation in the human // Genome Res. 2016. V. 26(6). P. 756–767. https://doi.org/10.1101/gr.196139.115
  87. Sanchez-Delgado M., Riccio A., Eggermann T. et al. Causes and consequences of multi-locus imprinting disturbances in humans // Trends Genet. 2016. V. 32(7). P. 444–455. https://doi.org/10.1016/j.tig.2016.05.001
  88. Xu D., Zhang C., Li J. et al. Polymorphic imprinting of SLC38A4 gene in bovine placenta // Biochem. Genet. 2018. V. 56(6). P. 639–649. https://doi.org/10.1007/s10528-018-9866-5
  89. Sanli I., Feil R. Chromatin mechanisms in the developmental control of imprinted gene expression // Int. J. Biochem. Cell Biol. 2015. V. 67. P. 139–147. https://doi.org/10.1016/j.biocel.2015.04.004
  90. Саженова Е.А., Никитина Т.В., Скрябин Н.А. и др. Эпигенетический статус импринтированных генов в плаценте при привычном невынашивании беременности // Генетика. 2017. Т. 53. № 3. С. 364–377. https://doi.org/10.7868/s0016675817020096
  91. Sazhenova E.A., Nikitina T.V., Vasilyev S.A. et al. NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss // J. Assisted Reprod. Genet. 2021. V. 38(11). P. 2893–2908. https://doi.org/10.1007/s10815-021-02312-z
  92. Hirasawa R., Chiba H., Kaneda M. et al. Maternal and zygotic dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development // Genes Dev. 2008. V. 22. P. 1607–1616. https://doi.org/10.1101/gad.1667008
  93. Wyns C., De Geyter C., Calhaz-Jorge C. et al. ART in Europe, 2017: Results generated from European registries by ESHRE. European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE) // Hum. Reprod. Open. 2021. V. 2021(3). P. e026. https://doi.org/10.1093/hropen/hoab026
  94. Kobayashi H. Canonical and non-canonical genomic imprinting in rodents // Front. Cell Dev. Biol. 2021. V. 9. P. e713878. https://doi.org/10.3389/fcell.2021.713878

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