Mechanisms of human DNA methylation, alteration of methylation patterns in physiological processes and oncology

DNA methylation is one of the epigenetic modifications of the genome, the essence of which is the attachment of a methyl group to nitrogenous bases. In the eukaryote genome, cytosine is methylated in the vast majority of cases. About 98% of cytosines are methylated as part of CpG dinucleotides. They, in turn, form CpG islands, which are clusters of these dinucleotides. Islands located in the regulatory elements of genes are in particular interest. They are assumed to play an important role in the regulation of gene expression in humans. Besides that, cytosine methylation serves the functions of genomic imprinting, transposon suppression, epigenetic memory maintenance, X- chromosome inactivation, and embryonic development. Of particular interest are the enzymatic processes of methylation and demethylation. The methylation process always depends on the work of enzymatic complexes and is very precisely regulated. The methylation process largely depends on the functioning of three groups of enzymes: writers, readers and erasers. Writers include proteins of the DNMT family, readers are proteins containing the MBD, BTB/POZ or SET- and RING-associated domains and erasers are proteins of the TET family. Whereas demethylation can be performed not only by enzymatic complexes, but also passively during DNA replication. Hence, the maintenance of DNA methylation is important. Changes in methylation patterns are observed during embryonic development, aging, and cancers. In both aging and cancer, massive hypomethylation of the genome with local hypermethylation is observed. In this review, we will review the current understanding of the mechanisms of DNA methylation and demethylation in humans, the structure and distribution of CpG islands, the role of methylation in the regulation of gene expression, embryogenesis, aging, and cancer development.

Automated summary

DNA methylation is an important epigenetic modification that involves the attachment of a methyl group to nitrogenous bases. In the majority of cases, cytosine is methylated, specifically in CpG dinucleotides that form CpG islands. These islands, particularly those located in gene regulatory elements, play a crucial role in gene expression regulation. Methylation serves various functions, such as genomic imprinting, transposon suppression, epigenetic memory maintenance, X-chromosome inactivation, and embryonic development. Understanding the mechanisms of DNA methylation and demethylation, the structure and distribution of CpG islands, and the role of methylation in gene regulation, embryogenesis, aging, and cancer development is essential.