Epigenetic Activation of Ribosomal Cistrons in Chromatids of Acrocentric Chromosome 15 in Lung Cancer

• Published in: Cytology and genetics 2021-09, Vol.55 (5), p.491-497
• Main Authors: Lezhava, T., Buadze, T., Mikaia, N., Jokhadze, T., Sigua, T., Gaiozishvili, M., Melkadze, T.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Chromatids; Chromosome 15; Chromosomes; Cistrons; Diagnosis; Epigenetics; Genomes; Heterochromatin; Human Genetics; Human Genome Project; Lung cancer; Nucleoli; Patients; rRNA; Structure-function relationships; Telomeres; Transcription
• ISSN: 0095-4527; 1934-9440
• DOI: 10.3103/S0095452721050042

After the Human Genome Project was declared complete, the strategic focus area of contemporary genetics shifted towards functional genomics whose research sphere comprises, among others, the study of noncoding DNA regions. The noncoding regions are located in heterochromatin. The functions of heterochromatin remain so far, to a considerable degree, unclear. The telomeres of the short arm of each human acrocentric chromosome (13, 14, 15, 21, 22) have satellite strands consisting of heterochromatin and are called nucleolar organizer regions (NORs). Human NORs contain from 250 to 670 copies of ribosomal RNA (rRNA) genes and only 50% of these copies are transcribed. Satellite strands in the chromatids of some acrocentric chromosomes are bound, forming “satellite associations” (SAs), which are always transcriptionally active. The phenomenon of SAs is a highly specific indicator for the structure and function of the nucleolus within the preceding interphase. In cancer, rDNA in the human genome may change. In this study, the epigenetic variability of ribosomal cistrons in lung cancer (LC) has been determined. It has been found that the frequency of chromatid SAs per cell was significantly higher (p < 0.05) in patients with LC (1.76 ± 0.08) than the analogous indicator in clinically healthy persons aged from 22 to 45 years (the control group) (1.35 ± 0.03). The associative activity in the chromatids of chromosome 15 group was lower (p < 0.01) than the activity in chromatids of other chromosomes. In contrast to the control group, the chromatids of chromosome 15 in the LC patients showed higher activity ( p < 0.05) of inclusion into associations than chromatids of other acrocentric chromosomes, which corresponded to the order: 15 > 13 = 14 > 21 > 22. A similar phenomenon was observed for the associations of chromatids of homologous chromosomes (15:15) in patients with LC, which significantly exceeded the indicator for this type of SA in healthy middle-aged individuals ( p < 0.001). The results have shown that the differential activity of satellite strands in the chromatids of chromosome 15 in patients with LC is characterized by epigenetic variability, which underlines the importance of studying SAs in terms of diagnosis and treatment strategy. The study of epigenetic variability in the activity of ribosomal cistrons in acrocentric chromatids in pathologies is a new medical area aiming at the diagnosis of diseases and determining new treatment strategies in the futu