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Epigenetic Changes of Activity of the Ribosomal Cistrons of Human Acrocentric Chromatids in Fetuses, Middle-aged (22–45 years) and Old Individuals (80–106 years)

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The level of total heterochromatin, Ag-positive nucleolar organiser regions (NORs) heterochromatin, non-associated and associated heterochromatin satellite stalks of acrocentric chromatids (some acrocentric chromosomal chromatid satellite stalks are connected to each other forming a satellite association), the intensity of each acrocentric chromatid involved in the association and types of associated chromatids were studied from 29 fetuses, from 32 healthy individuals 22–45 years (middle-aged) old and 22 healthy individuals 80–106 years old. The chromosomes were identified by the analysis of G-banding, using the Ikaros karyotyping system (Meta system). The differential scanning calorimeter showed an increase in chromatin thermostability (heterochromatinization) at adults (middle and old aged) compared with fetuses. The number of Ag-positive NORs per cell, for both associated and non-associated chromatids, was significantly increased in fetus cells than in middle and in extreme old age. The chromatid satellite association of fetus cells and the elderly was consistently reduced, compared with middle-aged individuals. Activity of chromatids of the 15th chromosomes, entered in association in the fetus, in middle and old age adults, was significantly reduced (p < 0.05), compared to other acrocentric chromatids, while the chromatids of 21st chromosome participated in associations with high activity (p < 0.05). The frequency of association of homologous (13:13; 14:14; 15:15; 22:22) and certain types of non-homologous chromatids (15:22 and 21:22) in the fetus and in 22–45 and 80–106 years old individuals was almost identically. The above noted phenomena apparently indicate that chromatid satellite ribosomal genes of acrocentric chromosomes undergo specific epigenetic variation depending on age, determining the specific synthesis of rRNA for constructing specific ribosomes, which may have great importance in assessing the general functioning of cells in normal and pathological conditions.

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  1. Bártová, E., Harničarová, Horáková, A., Uhlířová, R., Raška, I., Galiová, G., Orlova, D., and Kozubek, S., Structure and epigenetics of nucleoli in comparison with non-nucleolar compartments, J. Histochem. Cytochem., 2010, vol. 58, no. 5, pp. 391–403.

  2. Lyapunova, N., and Veiko, N., Ribosomal genes in the human genome: identification of four fractions, their organization in the nucleolus and metaphase chromosomes, Genetika, 2010, vol. 46, no. 9, pp. 1205–1209.

    Google Scholar 

  3. Dimitrova, D., DNA replication initiation patterns and spatial dynamics of the human ribosomal RNA gene loci, J. Cell Sci., 2011, vol. 16, pp. 2743–2752.

    Article  CAS  Google Scholar 

  4. Schmitz, K., Schmitt, N., Hoffmann-Rohrer, U., Schдfer, A., Grummt, I., and Mayer, Ch., TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation, Mol. Cell, 2009, vol. 33, pp. 344–353.

    Article  CAS  PubMed  Google Scholar 

  5. Mazin, A., Suicidal function of DNA methylation in age-related genome disintegration, Ageing Res. Rev., 2009, vol. 8, no. 4, pp. 314–327.

    Article  CAS  PubMed  Google Scholar 

  6. McStay, B. and Grummt, I., The epigenetics of rRNA genes: from molecular to chromosome biology, Ann. Rev. Cell. Dev. Biol., 2008, vol. 24, pp. 131–157.

    Article  CAS  Google Scholar 

  7. Lezhava, T., Monaselidze, J., Jokhadze, T., and Gaiozishvili, M., Epigenetic Regulation of “age” heterochromatin by peptide bioregulator cortagen, Int. J. Pept. Res. Ther., 2015, vol. 21, pp. 157–163.

    Article  CAS  Google Scholar 

  8. Lezhava, T., Jokhadze, T., Monaselidze, J., The functioning of “aged” heterochromatin, in Senescence, Intech Open Science, 2012, chapter 26, pp. 631–646. ISBN 978-953-51-0144-4.

    Google Scholar 

  9. Kikalishvili, L., Ramishvili, M., Nemsadze, G., Lezhava, T., Khorava, P., Gorgoshidze, M., Kiladze, M., and Monaselidze, J., Thermal stability of blood plasma proteins of breast cancer patients, DSC study, J. Therm. Anal. Calorim., 2015, vol. 120, no. 1, pp 501–505.

    Article  CAS  Google Scholar 

  10. Kobzar, A.I., Applied Mathematical Statistics. For Engineers and Scientists, Moscow: Fizmatlit, 2006.

    Google Scholar 

  11. Olson, M., The Nucleolus, Springer Sci. LTC, 2011.

    Book  Google Scholar 

  12. Tiku, V. and Antebi, A., Nucleolar Function in life span regulation, Trends Cell Boil., 2018, vol. 28, no. 8, pp. 662–672.

    Article  CAS  Google Scholar 

  13. Xu, B., Li, H., Perry, J., Singh, V.P., Unruh, J., Yu, Z., Zakari, M., McDowell, W., Li, L., and Gerton, J.L., Ribosomal DNA copy number loss and sequence variation in cancer, PLoS Genet., 2017, vol. 13, no. 6, e1006771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kim, J., Dilthey, A., Nagaraja, R., Lee, H.-Sh., Koren, S., Dudekula, D., Wood III, W.H., Piao, Y., Ogurtsov, A.Y., Utani, K., Noskov, V.N., Shabalina, S.A., Schlessinger, D., Phillippy, A.M., and Larionov, V., Variation in human chromosome 21 ribosomal RNA genes characterized by TAR cloning and long-read sequencing, Nucleic Acids Res., 2018, vol. 46, pp. 6712–6725.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Parks, M., Kurylo, C., Dass, R., Bojmar, L., Lyden, D., Vincent, C.Th., and Blanchard, S.C., Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression, Sci. Adv., 2018, vol. 4, no. 2, eaao0665.

  16. Porokhovnik, L. and Gerton, J., Ribosomal DNA-connecting ribosome biogenesis and chromosome biology, Chromosome Res., 2019, vol. 27, no. 1–2, pp. 1–3.

    Article  CAS  PubMed  Google Scholar 

  17. Villicaca, C., Cruz, G., and Zurita, M., The basal transcription machinery as a target for cancer therapy, Cancer Cell Int., 2014, vol. 14, no. 1, p. 18.

    Article  CAS  Google Scholar 

  18. Dai, M., Zeng, S., Jin, Y., Sun, X.X., David, L., and Lu, H., Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition, Mol. Cell, 2011, vol. 40, pp. 216–227.

    Google Scholar 

  19. Nćmeth, A. and Längst, G., Genome organization in and around the nucleolus, Trends Genet., 2011, vol. 27, no. 4, pp 149–156.

    Article  CAS  Google Scholar 

  20. Hirota, K., Miyoshi, T., Kugou, K., Hoffman, C., Shibata, T., and Ohta, K., Stepwise chromatin remodeling by a cascade of transcription initiation of non-coding RNA, Nature, 2008, vol. 456, pp.130–134.

    Article  CAS  PubMed  Google Scholar 

  21. Salminen, A. and Kaarniranta, K., SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree, Biochem. Biophys. Res. Commun., 2009, vol. 378, no. 1, pp. 6–9. doi 10.1016/j.bbrc.2008.11.023

  22. Lemos, B., Araripe, L., and Hartl, D., Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences, Science, 2008, vol. 319, no. 5859, pp. 91–93.

    Article  CAS  PubMed  Google Scholar 

  23. Boulon, S., Westman, B., Hutten, S., Boisvert, F.M., and Lamond, A.I., The nucleolus under stress, Mol. Cell., 2010, vol. 40, no. 2, pp. 216–227.

  24. Donati, G., Montanaro, L., and Derenzini, M., Ribosome biogenesis and control of cell proliferation: p53 is not alone, Cancer Res., 2012, vol. 72, no. 7, pp. 1602–1607.

    Article  CAS  PubMed  Google Scholar 

  25. Caudron-Herger, M., Pankert, T., Seiler, J., Nćmeth, A., Voit, R., Grummt, I., and Rippe, K., Alu element-containing RNAs maintain nucleolar structure and function, EMBO J., 2015, vol. 34, no. 22, pp. 2758–2774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cong, R., Das, S., Ugrinova, I., Kumar, S., Mongelard, F., Wong, J., and Bouvet, Ph., Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase 1 transcription, Nucleic Acids Res., 2012, vol. 40, no. 19, pp. 9441–9454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Barsaglieri, C. and Santoro, R., Genome organization in and around the nucleolus, Cells, 2019, vol. 8, no. 6, pii: E579.

    Article  CAS  Google Scholar 

  28. Caudron-Herger, M., Diederichs, S., Mitochondrial mutations in human cancer: curation of translation, RNA Biol., 2018, vol. 15, no. 1, pp. 62–9.

    Article  PubMed  Google Scholar 

  29. Allshire, R. and Madhani, H., Ten principles of heterochromatin formation and function, Nat. Rev. Mol. Cell Biol., 2018, vol. 19, no. 4, pp. 229–244.

    Article  CAS  PubMed  Google Scholar 

  30. Baranov, V. and Kuznecova, T., Cytogenetics of Human Embryonic Development, St. Petersburg: Nauka, 2006.

    Google Scholar 

  31. Mayer, C. and Grummt, I., Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases, Oncogene, 2006, vol. 25, no. 48, pp. 6384–6391.

    Article  CAS  Google Scholar 

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Correspondence to T. Lezhava, J. Monaselidze, N. Sigua or M. Koridze.

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The research was financed by Ivane Javakhishvili Tbilisi State University.


Conflict of interest. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. The Ethical Committee of the Tbilisi State Medical University (TSMU), Georgia approved the protocol and the parents of each fetus, and all adults 22-106 years provided informed consent.


Professor Teimuraz Lezhava Planned the research. Dr. Tamar Buadze, Associated Professor Tinatin Jokhadze and Assistant-Professor Maia Gaiozishvili have made experimental part of the research – cultivation and analyzing of chromosomes. Professor Jamlet Monaselidze made the Differential Scanning Calorimeter investigation. Professor Estate Khmaladze had made the statistical analysis of the data. Dr. Natela Jangulashvili, Dr. Nino Sigua and Maia Rukhadze participated in collection research material and analyzing of chromosomes from fetus. Professor M. Koridze and Nato Zosidze provided the collection of Blood from senile individuals.

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Lezhava, T., Buadze, T., Monaselidze, J. et al. Epigenetic Changes of Activity of the Ribosomal Cistrons of Human Acrocentric Chromatids in Fetuses, Middle-aged (22–45 years) and Old Individuals (80–106 years). Cytol. Genet. 54, 233–242 (2020).

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