Study of the Patterns of DNA Methylation in Human Cells Through the Prism of Intra-Strand DNA Symmetry

TL;DR

This study explores how DNA methylation patterns in human cells relate to intra-strand DNA symmetry, revealing non-random methylation and compensatory asymmetry during cell differentiation.

Contribution

The paper introduces a novel analysis of DNA methylation through the lens of intra-strand symmetry, uncovering compensatory asymmetry and non-random methylation patterns.

Findings

DNA methylation patterns deviate from Chargaff’s Second Parity Rule, showing methylation asymmetry in reverse-complementary oligomers.

Compensatory methylation asymmetry reduces deviations from intra-strand symmetry during cell differentiation.

Four out of six tetranucleotide pairs show pronounced methylation asymmetry, possibly linked to chromosome folding and 3D genome structure.

Abstract

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.

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