Epigenetic modification under the influence of peptide bioregulators on "aged" heterochromatin.

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.