DNA-Methylation

DNA methylation is the classic epigenetic mechanism in which a methyl group is attached to a nitrogen-containing base. Although both cytosine and adenine can be targets, cytosine methylation, in which a methyl group attaches to the fifth carbon of cytosine to form 5-methylcytosine (5mC), is widespread in mammalian genomes (Ehrlich M et al. 1981). DNA methylation occurs most frequently at symmetrical CpG dinucleotides. About 70-80 % of the CpG sites in the mammalian genome are methylated in most somatic tissues (Doskocil J et al. 1962).

DNA methylation is a chemical modification of DNA in which small methyl groups (-CH₃) are attached to certain bases, usually to cytosine residues within so-called CpG dinucleotides. DNA methylation determines when and where genes are active without changing the DNA sequence itself. This regulates the development, function and adaptability of cells. Abnormal DNA methylation can indicate disease states, including cancer.

The basic principle of DNA methylation: the site of modification is mainly cytosine, which is located before a guanine (CpG sites). DNA methyltransferases (DNMTs) transfer the methyl group from S-adenosylmethionine to cytosine.

Effects on gene activity: The base sequence of the DNA does not change during this process, but the methyl groups act like a switch principle. Heavily methylated promoter regions are less easily recognized by transcription factors, making the gene in question more difficult to read (transcriptional repression).

Biological functions / purpose: Gene regulation and cell differentiation: During development, certain genes are specifically switched on or off.

Imprinting: For some genes, only the maternal or paternal copy is active, controlled by methylation.

X chromosome inactivation: In female mammals, one of the two X chromosomes is largely silenced.

Protection of the genome: Methylation suppresses transposons ("jumping genes") and contributes to genomic stability.

Dynamics and reversibility: Methylation patterns can change through active demethylation (e.g. TET enzymes) or during replication. Environmental factors such as nutrition, stress or toxins can influence these patterns ("epigenetic imprinting").