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Epigenetics changes of activity of the ribosomal cistrons of acrocentric chromatids in fetus, middle age (25–40 years) and old individuals (88–106 years)
SUMMARY. The level of total heterochromatin, Ag-positive nucleolar organizer regions (NORs), 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 were studied in 29 fetuses, 32 healthy 22–45-year-old individuals (middle-aged) and 22 healthy 80–106-year-old individuals. 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) in adults (middle-aged and elderly) compared with fetuses. The number of Ag-positive NORs per cell, for both associated and non-associated chromatids, was significantly increased in fetus cells compared to middle age and to extreme old age. The number of satellite associations of chromatids per cell in the fetus and in individuals of the senile group was reduced, compared with middle-aged individuals. The activity of entering the chromatid associations was significantly lower for 15th chromosome in all the studied groups compared to other acrocentric chromatids, while the chromatids of the 21st chromosome participated in associations with high activity. The frequency of associations of homologous chromosome chromatids (13:13; 14:14; 15:15 and 22:22) and of certain types of chromosome chromatids (15:22 and 21:22) in the fetus, middle-aged individuals and in the senile group was almost identical. The above phenomena seem to indicate that the ribosomal genes of chromatid satellite stalks undergo a specific epigenetic variability depending on the age, determining specific rRNA syntheses for the construction of specific ribosomes which may have great importance in assessing the overall functioning of cells in normal and pathological conditions.
Key words: Aging, Association, Heterochromatinization, Fetuses, Ribosomal genes, Satellite stalks
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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. https://doi.org/10.1369/jhc.2009.955435
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.
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. https://doi.org/10.1242/jcs.082230
4. Schmitz, K., Schmitt, N., Hoffmann-Rohrer, U., Schäfer, 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. https://doi.org/10.1016/j.molcel.2009.01.015
5. Mazin, A., Suicidal function of DNA methylation in age-related genome disintegration, Ageing Res. Rev., 2009, vol. 8, no. 4, pp. 314–327. https://doi.org/10.1016/j.arr.2009.04.005
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. https://doi.org/10.1146/annurev.cellbio.24.110707.175259
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.
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.
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.
10. Kobzar, A.I., Applied Mathematical Statistics. For Engineers and Scientists, Moscow: Fizmatlit, 2006.
11. Olson, M., The Nucleolus, Springer Sci. LTC, 2011.
12. Tiku, V. and Antebi, A., Nucleolar Function in life span regulation, Trends Cell Boil., 2018, vol. 28, no. 8, pp. 662–672. https://doi.org/10.1016/j.tcb.2018.03.007
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. https://doi.org/10.1371/journal.pgen.1006771
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. https://doi.org/10.1093/nar/gky442
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. https://doi.org/10.1126/sciadv.aao0665
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. https://doi.org/10.1007/s10577-018-9601-4
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. https://doi.org/10.1186/1475-2867-14-18
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.
19. Nćmeth, A. and Längst, G., Genome organization in and around the nucleolus, Trends Genet., 2011, vol. 27, no. 4, pp 149–156. https://doi.org/10.1016/j.tig.2011.01.002
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. https://doi.org/10.1038/nature07348
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. https://doi.org/10.1126/science.1148861
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.https://doi.org/10.1016/j.molcel
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. https://doi.org/10.1158/0008-5472.CAN-11-3992
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. https://doi.org/10.15252/embj.201591458
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. https://doi.org/10.1093/nar/gks720
27. Barsaglieri, C. and Santoro, R., Genome organization in and around the nucleolus, Cells, 2019, vol. 8, no. 6, pii: E579. https://doi.org/10.3390/cells8060579
28. Caudron-Herger, M., Diederichs, S., Mitochondrial mutations in human cancer: curation of translation, RNA Biol., 2018, vol. 15, no. 1, pp. 62–9. https://doi.org/10.1080/15476286.2017.1373239
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. https://doi.org/10.1038/nrm.2017.119
30. Baranov, V. and Kuznecova, T., Cytogenetics of Human Embryonic Development, St. Petersburg: Nauka, 2006.
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.
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