1Tbilisi State University, Department of Genetics; 2Tbilisi State University, Institute of Genetics; Georgia.
2Tbilisi State University, Institute of Genetics;3E.Andronikashvili Institute of Physics, Laboratory of Physics, Tbilisi, Georgia.
Georgian Med News. 2020 Dec(309):120-124.
Following the completion of the Human Genome Project, the strategic direction of modern genetics has moved toward functional genomics, to explore the functions of non-coding regions of DNA. These non-coding regions are localized in heterochromatin. The functions of heterochromatin largely remain unclear. Facultative heterochromatin occurs in aging. The effect of synthetic peptide bioregulators (tetrapeptides: Ala-Glu-Asp-Gly; Lys-Glu-Asp-Ala; Ala-Glu-Asp-Pro and dipeptide - Lys-Glu) on total heterochromatin, constitutive (structural) and facultative heterochromatin in cultured lymphocytes of individuals aged 75-88 and 20 - 40 years have been studied. We used a molecular-cytogenetic methods: differential scanning calorimetry; activity of ribosomal genes of acrocentric chromosome satellite stalks - NORs; C-heterochromatin; sister chromatid exchanges (SCE). The results showed that peptide bioregulators: 1. induce unrolling - deheterochromatinization of total heterochromatin, constitutive (pericentromeric, telomeric, and nucleolar organizer regions (NOR)) and facultative heterochromatin; 2. induce higher level of SCEs (deheterochromatinization), were registered in telomeric heterochromatin and decreased (heterochromatinization) SCEs level in the medial regions of chromosome arms; 3. each peptide bioregulator selectively deheterochromatinizes a specific region of chromosomes releasing inactive (once active) genes, which, apparently, can contribute to the targeted treatment of aging diseases. The proposed genetic mechanism responsible for the remodeling of constitutive and facultative heterochromatin emphasizes the importance of external and internal factors in the development of diseases and may lead to the development of a strategy for the therapeutic treatment of senile pathology.
在人类基因组计划完成之后，现代遗传学的战略方向转向了功能基因组学，以探索 DNA 中非编码区域的功能。这些非编码区域定位于异染色质中。异染色质的功能在很大程度上仍不清楚。兼性异染色质发生在衰老过程中。研究了合成肽生物调节剂（四肽：Ala-Glu-Asp-Gly；Lys-Glu-Asp-Ala；Ala-Glu-Asp-Pro 和二肽 - Lys-Glu）对培养的 75-88 岁和 20-40 岁个体的淋巴细胞总异染色质、组成型（结构）异染色质和兼性异染色质的影响。我们使用了分子细胞遗传学方法：差示扫描量热法；着丝粒染色体卫星柄的核糖体基因活性 - NORs；C-异染色质；姐妹染色单体交换 (SCE)。结果表明，肽生物调节剂：1. 诱导展开 - 总异染色质、组成型（着丝粒周围、端粒和核仁组织者区域 (NOR)）和兼性异染色质的去异染色质化；2. 诱导更高水平的 SCE（去异染色质化），在端粒异染色质中记录到，而在染色体臂的中部区域中 SCE 水平降低（异染色质化）；3. 每种肽生物调节剂都选择性地去异染色质化染色体的特定区域，释放非活性（曾经是活性的）基因，这显然有助于针对衰老疾病的靶向治疗。负责构建性和兼性异染色质重塑的提出的遗传机制强调了外部和内部因素在疾病发展中的重要性，并可能导致针对衰老病理学的治疗治疗策略的发展。
