Epigenetic Mechanisms of Peptidergic Regulation of Gene Expression during Aging of Human Cells

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V. V. Ashapkin^1*, N. S. Linkova^2,3, V. Kh. Khavinson^2,4, and B. F. Vanyushin¹

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-3181; E-mail: ashapkin@genebee.msu.ru

²St. Petersburg Institute of Bioregulation and Gerontology, 197110 St. Petersburg, Russia; fax: (812) 230-0049; E-mail: linkova@gerontology.ru

³St. Petersburg State Polytechnical University, 195251 St. Petersburg, Russia; fax: (812) 552-6080; E-mail: linkova@medfiz.ru

⁴Mechnikov North-West State Medical University, 191015 St. Petersburg, Russia; fax: (812) 303-5035; E-mail: khavinson@gerontology.ru

^* To whom correspondence should be addressed.

Received July 29, 2014; Revision received September 13, 2014

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Expression levels of genes encoding specific transcription factors and other functionally important proteins vary upon aging of pancreatic and bronchial epithelium cell cultures. The peptides KEDW and AEDL tissue-specifically affect gene expression in pancreatic and bronchial cell cultures, respectively. It is established in this work that the DNA methylation patterns of the PDX1, PAX6, NGN3, NKX2-1, and SCGB1A1 gene promoter regions change upon aging in pancreatic and bronchial cell cultures in correlation with variations in their expression levels. Thus, stable changes in gene expression upon aging of cell cultures could be caused by changes in their promoter methylation patterns. The methylation patterns of the PAX4 gene in pancreatic cells as well as those of the FOXA1, SCGB3A2, and SFTPA1 genes in bronchial cells do not change upon aging and are unaffected by peptides, whereas their expression levels change in both cases. The promoter region of the FOXA2 gene in pancreatic cells contains a small number of methylated CpG sites, their methylation levels being affected by cell culture aging and KEDW, though without any correlation with gene expression levels. The promoter region of the FOXA2 gene is completely unmethylated in bronchial cells irrespective of cell culture age and AEDL action. Changes in promoter methylation might be the cause of age- and peptide-induced variations in expression levels of the PDX1, PAX6, and NGN3 genes in pancreatic cells and NKX2-1 and SCGB1A1 genes in bronchial cells. Expression levels of the PAX4 and FOXA2 genes in pancreatic cells and FOXA1, FOXA2, SCGB3A2, and SFTPA1 genes in bronchial cells seem to be controlled by some other mechanisms.

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KEY WORDS: short peptides, DNA methylation, transcription, cell differentiation, pancreatic cell culture, bronchial cell culture, differentiation factors

DOI: 10.1134/S0006297915030062

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