Dna methylation

DNA methylation is an important mechanism for the regulation of gene expression. It is also an important molecular biological, epigenetic tool. DNA methylation does not cause a genetic mutation, but only a modification of the gene.

DNA methylation occurs in many organisms and has various biological functions. The sequence of DNA methylation is based on the corresponding pattern of the mother cell and is then part of the epigenetic code of a cell.

During DNA methylation, certain enzymes, the DNA methyl transferases (DMT), transfer a methyl group to defined cytosine molecules of the DNA double strand. The methylation takes place mainly on so-called CpG dinucleotides (CpG stands for cytosine phosphatidyl guanine). CG pairs, which are located at the beginning of a gene, are particularly frequently methylated. Methylation at this site usually prevents transcription of the gene by the RNA polymerase.

The methyl-releasing enzyme DNA demethylase has also been identified. Thus, the methylation of DNA is not a one-way street, but the state of methylation can be regulated depending on cell function.

The methyl-binding protein (MeCP) can attach itself to methylated DNA. This process is in turn the starting point for further protein attachment, which leads to the modification of histones and ultimately to the inactivation of a chromosomal segment.

So far, 3 human DNA methyltransferases are known:

• DNMT1
• DNMT3a and
• DNMT3b (Note: DNMT2 methylated RNA).

Maintenance methylation: DNMT1 is responsible for maintenance methylation during cell division. During DNA duplication before each cell division, certain nucleotides of the old DNA strand are methylated. However, the newly formed DNA strand is not yet methylated. This difference is compensated by DNMT1.

New methylation (de novo methylation): The methyltransferases DNMT3a and DNMT3b methylate the CG-dimers, which are remethylated due to cell differentiation (de novo methylation). New methylation is particularly common in the early stages of mammalian embryonic development.

Unmethylated cytidines are susceptible to deamination. In this process the amino group at position 4 of the ring is removed from the cytidines. A deaminated non-methylated cytidine is an uracil. This is not one of the 4 physiological DNA bases "adenine, cytosine, guanine or thymine". Therefore an uracil in the DNA is recognized as a defect and eliminated.

If a 5-methylcytidine is deaminated, thymine is formed. Thymine is a DNA building block. This means that the DNA repair system does not recognize whether this thymine or the opposite guanine was inserted incorrectly. The error is not recognized. The thymine is not eliminated. If this methylation has taken place in a germ cell, this mutation is also inherited.

DNA methylation and epigenetics: A number of environmental factors such as stress, smoking (influence on histone acetylation), various drugs(glucocorticoids, theophylline) can change the methylation pattern of a person, so that certain genes are activated while others are inactivated. Epigenetic mechanisms play a role in tumour development, e.g. by silencing tumour suppressor genes. In allergological diseases, connections between environmental pollution and DNA methylation behaviour are assumed.

1. Head JA (2014) Patterns of DNA methylation in animals: an ecotoxicological perspective. Integr Comp Biol 54:77-86.
2. Jeltsch A et al (2014) New concepts in DNA methylation. Trends Biochem Sci 39:310-318.
3. Moore LD et al (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23-38.