Study of the Patterns of DNA Methylation in Human Cells Through the Prism of Intra-Strand DNA Symmetry
Ramazanova Z. Alikul A. Begimbetova D. Taipakova S. Matkarimov B.T. Saparbaev M.
October 2025Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2025#26Issue 19
Cellular organisms store heritable information in two forms, genetic and epigenetic, the latter being largely dependent on cytosine methylation (5mC). Chargaff’s Second Parity Rule (CSPR) describes the nucleotide composition of cellular genomes in terms of intra-strand DNA symmetry. However, it remains unknown whether DNA methylation patterns display intra-strand DNA symmetry. Computational analysis was conducted of the DNA methylation patterns observed in human cell lines and in tissue samples from healthy donors. Analysis of 5mC marks in mutually reverse-complementary pairs of short oligomers, containing CpG dinucleotide in the middle, revealed deviations from CSPR and methylation asymmetry that can be observed for two non-overlapping mirror groups defined by CpG methylation values. Deviations from CSPR, together with combinatorial probabilities of pattern distributions and computer simulations, highlight the non-random nature of methylation processes and enabled us to identify specific cell types as outliers. Further analysis revealed a compensatory methylation asymmetry that reduces deviations from intra-strand symmetry and implies the existence of strand-specific methylation during cell differentiation. Among six pairs of reverse-complementary tetranucleotides, four pairs with specific sequence motifs display pronounced methylation asymmetry. This mirror asymmetry may be associated with chromosome folding and the formation of a complex three-dimensional landscape.
5-methylcytosine , cell differentiation , Chargaff’s Second Parity Rule , DNA methylation , epigenetics , human cell types , intra-strand DNA symmetry
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National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Molecular Biology and Genetics, Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Scientific Research Institute of Biology and Biotechnology Problems, Al-Farabi Kazakh National University, Almaty, 050040, Kazakhstan
Faculty of Information Technology, L.N. Gumilev Eurasian National University, Astana, 010000, Kazakhstan
Groupe «Mechanisms of DNA Repair and Carcinogenesis», CNRS UMR9019, Université Paris-Saclay, Gustave Roussy Cancer CampusCedex, Villejuif, F-94805, France
National Laboratory Astana
Department of Molecular Biology and Genetics
Scientific Research Institute of Biology and Biotechnology Problems
Faculty of Information Technology
Groupe «Mechanisms of DNA Repair and Carcinogenesis»
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