Skip to main content
SpringerLink
Log in

Methylation status of LINE-1 retrotransposon in chromosomal mosaicism during early stages of human embryonic development

  • Cell Molecular Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Early stages of human embryonic development are characterized by the spatiotemporal coincidence of events of total epigenetic genome reprogramming and elevated level of mosaic forms of numerical chromosome abnormalities. It is possible that the abnormal reprogramming of various regions of the genome can lead to violations of local epigenetic chromatin organization and gene expression, which affect the correct chromosome segregation during mitosis. In this study, a comparative analysis of the methylation index of LINE-1 retrotransposon, which largely reflects the methylation profile of the genome, is performed in placental tissues of spontaneous abortions with complete and mosaic forms of aneuploidy and with a normal karyotype, as well as in the control group of induced abortions of the first trimester of pregnancy. It was shown that extraembryonic mesoderm and chorionic cytotrophoblast of spontaneous abortions with chromosomal mosaicism are characterized by the highest index of LINE-1 methylation among all studied groups. At the same time, the excessive hypomethylation of transposable genetic element was registered in spontaneous abortions with normal karyotype. We hypothesize that violations of parental genome demethylation during epigenetic reprogramming at preimplantation stages of development may be associated with an increased frequency of mitotic errors in chromosome segregation, which leads to the formation of a mosaic karyotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

EM:

extraembryonic mesoderm

CT:

cytotrophoblast

References

  1. Smith Z.D., Chan M.M., Mikkelsen T.S., Gu H., Gnirke A., Regev A., Meissner A. 2012. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature. 484, 339–344.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Vanneste E., Voet T., Le Caignec C., Ampe M., Konings P., Melotte C., Debrock S., Amyere M., Vikkula M., Schuit F., Fryns J.P., Verbeke G., D’Hooghe T., Moreau Y., Vermeesch J.R. 2009. Chromosome instability is common in human cleavage-stage embryos. Nature Med. 15, 577–583.

    Article  CAS  PubMed  Google Scholar 

  3. Kashevarova A.A., Tolmacheva E.N., Sukhanova N.N., Sazhenova E.A., Lebedev I.N. 2009. Estimation of the methylation status of the promoter region of the cell cycle control gene P14APF in placental tissues of spontaneous abortions with chromosomal mosaicism. Russ. J. Genet. 45, 749–755.

    Article  CAS  Google Scholar 

  4. Kashevarova A.A., Tolmacheva E.N., Sazhenova E.A., Sukhanova N.N., Lebedev I.N. 2011. Epigenetic status of cell cycle regulation genes in the placenta of human embryos with chromosomal mosaicism. Mol. Biol. (Moscow). 45, 283–290.

    Article  CAS  Google Scholar 

  5. Kashevarova A.A. 2010. Cytogenetic characteristics and epigenetic mechanisms of chromosome mosaicism formation in human embryonic development. Extended abstract of Cand. Sci. (Biol.) Dissertation. Tomsk: Inst. Med. Genet., 2010.

    Google Scholar 

  6. Tolmacheva E.N., Kashevarova A.A., Sukhanova N.N., Kharkov V.N., Lebedev I.N. 2011. Skewed X-chromosome inactivation in human embryos with mosaic trisomy 16. Russ. J. Genet. 47, 354–357.

    Article  CAS  Google Scholar 

  7. Tolmacheva E.N., Kashevarova A.A., Skryabin N.A., Lebedev I.N. 2013. Epigenetic effects of trisomy 16 in human placenta. Mol. Biol. (Moscow). 47, 373–381.

    Article  CAS  Google Scholar 

  8. Blair J.D., Langlois S., McFadden D.E., Robinson W.P. 2014. Overlapping DNA methylation profile between placentas with trisomy 16 and early-onset preeclampsia. Placenta. 35, 216–222.

    Article  CAS  PubMed  Google Scholar 

  9. Bollati V., Baccarelli A., Hou L., Bonzini M., Fustinoni S., Cavallo D., Byun H.M., Jiang J., Marinelli B., Pesatori A.C., Bertazzi P.A., Yang A.S. 2007. Changes in DNA methylation patterns in subjects exposed to low-dose benzene. Cancer Res. 67, 876–880.

    Article  CAS  PubMed  Google Scholar 

  10. Rusiecki J.A., Baccarelli A., Bollati V., Tarantini L., Moore L.E., Bonefeld-Jorgensen E.C. 2008. Global DNA hypomethylation is associated with high serumpersistent organic pollutants in Greenlandic Inuit. Environ. Health Perspect. 116, 1547–1552.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Beraldi R., Pittoggi C., Sciamanna I., Mattei E., Spadafora C. 2006. Expression of LINE-1 retroposons is essential for murine preimplantation development. Mol. Reprod. Dev. 73, 279–287.

    Article  CAS  PubMed  Google Scholar 

  12. Tabano S., Colapietro P., Cetin I., Grati F.R., Zanutto S., Mandò C., Antonazzo P., Pileri P., Rossella F., Larizza L., Sirchia S.M., Miozzo M. 2010. Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction. Epigenetics. 5, 313–324.

    Article  CAS  PubMed  Google Scholar 

  13. Price E.M., Cotton A.M., Peñaherrera M.S., McFadden D.E., Kobor M.S., Robinson W. 2012. Different measures of “genome-wide” DNA methylation exhibit unique properties in placental and somatic tissues. Epigenetics. 7, 652–663.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Oda M., Oxley D., Dean W., Reik W. 2013. Regulation of lineage specific DNA hypomethylation in mouse trophectoderm. PLoS ONE. 8, e68846.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Tolmacheva E.N., Kashevarova A.A., Skryabin N.A., Lebedev I.N. 2011. DNA methylation profile in human placental tissues. Mol. Biol. (Moscow). 45, 493–499.

    Article  CAS  Google Scholar 

  16. Lebedev I.N., Ostroverkhova N.V., Nikitina T.V. Sukhanova N.N., Nazarenko S.A. 2004. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur. J. Hum. Genet. 12. 513–520.

    Article  CAS  PubMed  Google Scholar 

  17. Lander E.S., Linton L.M., Birren B., Nusbaum C., Zody M.C., Baldwin J., Devon K., Dewar K., Doyle M., FitzHugh W., Funke R., Gage D., Harris K., Heaford A., Howland J., Kann L., Lehoczky J., LeVine R., McEwan P., McKernan K., Meldrim J., Mesirov J.P., Miranda C., Morris W., Naylor J., Raymond C., Rosetti M., Santos R., Sheridan A., Sougnez C., Stange-Thomann N., Stojanovic N., Subramanian A., Wyman D., Rogers J., Sulston J., Ainscough R., Beck S., Bentley D., Burton J., Clee C., Carter N., Coulson A., Deadman R., Deloukas P., Dunham A., Dunham I., Durbin R., French L., Grafham D., Gregory S., Hubbard T., Humphray S., Hunt A., Jones M., Lloyd C., McMurray A., Matthews L., Mercer S., Milne S., Mullikin J.C., Mungall A., Plumb R., Ross M., Shownkeen R., Sims S., Waterston R.H., Wilson R.K., Hillier L.W., McPherson J.D., Marra M.A., Mardis E.R., Fulton L.A., Chinwalla A.T., Pepin K.H., Gish W.R., Chissoe S.L., Wendl M.C., Delehaunty K.D., Miner T.L., Delehaunty A., Kramer J.B., Cook L.L., Fulton R.S., Johnson D.L., Minx P.J., Clifton S.W., Hawkins T., Branscomb E., Predki P., Richardson P., Wenning S., Slezak T., Doggett N., Cheng J.F., Olsen A., Lucas S., Elkin C., Uberbacher E., Frazier M., Gibbs R.A., Muzny D.M., Scherer S.E., Bouck J.B., Sodergren E.J., Worley K.C., Rives C.M., Gorrell J.H., Metzker M.L., Naylor S.L., Kucherlapati R.S., Nelson D.L., Weinstock G.M., Sakaki Y., Fujiyama A., Hattori M., Yada T., Toyoda A., Itoh T., Kawagoe C., Watanabe H., Totoki Y., Taylor T., Weissenbach J., Heilig R., Saurin W., Artiguenave F., Brottier P., Bruls T., Pelletier E., Robert C., Wincker P., Smith D.R., Doucette-Stamm L., Rubenfield M., Weinstock K., Lee H.M., Dubois J., Rosenthal A., Platzer M., Nyakatura G., Taudien S., Rump A., Yang H., Yu J., Wang J., Huang G., Gu J., Hood L., Rowen L., Madan A., Qin S., Davis R.W., Federspiel N.A., Abola A.P., Proctor M.J., Myers R.M., Schmutz J., Dickson M., Grimwood J., Cox D.R., Olson M.V., Kaul R., Raymond C., Shimizu N., Kawasaki K., Minoshima S., Evans G.A., Athanasiou M., Schultz R., Roe B.A., Chen F., Pan H., Ramser J., Lehrach H., Reinhardt R., McCombie W.R., de la Bastide M., Dedhia N., Blöcker H., Hornischer K., Nordsiek G., Agarwala R., Aravind L., Bailey J.A., Bateman A., Batzoglou S., Birney E., Bork P., Brown D.G., Burge C.B., Cerutti L., Chen H.C., Church D., Clamp M., Copley R.R., Doerks T., Eddy S.R., Eichler E.E., Furey T.S., Galagan J., Gilbert J.G., Harmon C., Hayashizaki Y., Haussler D., Hermjakob H., Hokamp K., Jang W., Johnson L.S., Jones T.A., Kasif S., Kaspryzk A., Kennedy S., Kent W.J., Kitts P., Koonin E.V., Korf I., Kulp D., Lancet D., Lowe T.M., McLysaght A., Mikkelsen T., Moran J.V., Mulder N., Pollara V.J., Ponting C.P., Schuler G., Schultz J., Slater G., Smit A.F., Stupka E., Szustakowski J., Thierry-Mieg D., Thierry-Mieg J., Wagner L., Wallis J., Wheeler R., Williams A., Wolf Y.I., Wolfe K.H., Yang S.P., Yeh R.F., Collins F., Guyer M.S., Peterson J., Felsenfeld A., Wetterstrand K.A., Patrinos A., Morgan M.J., de Jong P., Catanese J.J., Osoegawa K., Shizuya H., Choi S., Chen Y.J.; International Human Genome Sequencing Consortium. 2001. Initial sequencing and analysis of the human genome. Nature. 409, 860–921.

    Article  CAS  PubMed  Google Scholar 

  18. Fedorov A.V. 2009. Regulation of mammalian LINE1 retrotransposon transcription. Cell Tissue Biol. 3, 1–13.

    Article  Google Scholar 

  19. Lane N., Dean W., Erhardt S., Hajkova P., Surani A., Walter J., Reik W. 2003. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis. 35, 88–93.

    Article  CAS  PubMed  Google Scholar 

  20. Pendina A.A., Efimova O. A., Fedorova I.D., Leont’eva O.A., Shilnikova E.M., Lezhnina J.G., Kuznetzova T.V., Baranov V.S. 2010. DNA methylation patterns of metaphase chromosomes in human preimplantation embryos. Cytogenetic Genome Res. 132, 1–7.

    Article  Google Scholar 

  21. Li E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nature Rev. Genet. 8, 662–673.

    Article  Google Scholar 

  22. Tolmacheva E.N., Kashevarova A.A., Sukhanova N.N., Sazhenova E.A., Lebedev I.N. 2008. Epigenetic inactivation of the RB1 gene as a factor of genomic instability: a possible contribution to etiology of chromosomal mosaicism during human embryo development. Russ. J. Genet. 44, 1266–1271.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institute of Medical Genetics, Siberian Branch, Russian Academy of Medical Sciences, Tomsk, 634050, Russia

    S. A. Vasilyev, E. N. Tolmacheva, A. A. Kashevarova, E. A. Sazhenova & I. N. Lebedev

  2. Laboratory of Human Ontogenetics, Tomsk State University, Tomsk, 634050, Russia

    S. A. Vasilyev, A. A. Kashevarova & I. N. Lebedev

Authors
  1. S. A. Vasilyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. N. Tolmacheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. A. Kashevarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. A. Sazhenova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. N. Lebedev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. A. Vasilyev.

Additional information

Original Russian Text © S.A. Vasilyev, E.N. Tolmacheva, A.A. Kashevarova, E.A. Sazhenova, I.N. Lebedev, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 1, pp. 165–174.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vasilyev, S.A., Tolmacheva, E.N., Kashevarova, A.A. et al. Methylation status of LINE-1 retrotransposon in chromosomal mosaicism during early stages of human embryonic development. Mol Biol 49, 144–152 (2015). https://doi.org/10.1134/S0026893314060193

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893314060193

Keywords

Search

Navigation