DNA methylation

Methylation is a chemical process in which a methyl group is transferred from one molecule to another. In the DNA methylation A methyl group couples to a certain part of the DNA and thus changes a building block of the genetic material.

What is DNA Methylation?

In DNA methylation, a methyl group attaches to certain nucleotides in the DNA. DNA, also known as DNA or deoxyribonucleic acid, is the carrier of genetic information. With the help of the information stored in the DNA, proteins can be produced.

The structure of the DNA corresponds to that of a rope ladder, whereby the stiles of the rope ladder are twisted in a helical manner, creating a so-called double helix structure. The side parts of the rope ladder are made from sugar and phosphate residues. The rungs of the rope ladder represent organic bases. The bases of DNA are adenine, cytosine, guanine and thymine.

Two bases each connect as a pair to form a rope ladder rung. The base pairs are each formed by two complementary bases: adenine and thymine as well as cytosine and guanine. A nucleotide is a molecule that is formed from a phosphate, a sugar and a base component. In DNA methylation, special enzymes, the methyltransferases, attach a methyl group to the base cytosine. This is how methylcytosine is created.

Function & task

The DNA methylations are considered markers that enable the cell to use or not use certain areas of the DNA. They represent a mechanism for gene regulation. One could therefore also call them an on / off switch, since in most cases methylation of a base prevents a copy of the gene concerned during the transcription of the DNA.

DNA methylation ensures that the DNA can be used in different ways without the DNA sequence itself changing. Methylation creates new information on the genome, i.e. the genetic material. One speaks of an epigenome and the process of epigenetics. The epigenome explains why different cells can generate identical genetic information. For example, a wide variety of tissue types can arise from human stem cells. A whole person can even emerge from the individual egg cell. The epigenome of the cell decides which form and function it takes on. The marked genes show the cell what to do for it. A muscle cell only uses the marked sections of DNA that are relevant to it for its work. Nerve cells, heart cells or cells in the lungs do the same.

The markings by the methyl groups are flexible. They can be removed or moved. This would make the previously deactivated DNA segment active again. This flexibility is necessary because there is a constant interplay between the genome and the environment. DNA methylation takes up these environmental influences.

DNA methylations can also be stable and are passed on from one generation of cells to the next. In a healthy body, only spleen cells can ever develop in the spleen. This ensures that the respective body can fulfill its tasks.

The epigenetic changes can not only be transferred from one cell to the next, but also from one generation to the next. For example, worms inherit immunity to certain viruses through DNA methylation.

Illnesses & ailments

Pathological changes in the epigenome have so far been detected in many diseases and identified as the cause of diseases in the fields of immunology, neurology and, in particular, oncology.

In tissues that are affected by cancer, defects in the DNA sequence and defects in the epigenome are almost always found. An abnormal pattern of DNA methylation is often seen in tumors. The methylation can be increased or decreased. Both have far-reaching consequences for the cell. In the event of increased methylation, i.e. hypermethylation, so-called tumor suppressor genes can be inactivated. Tumor suppressor genes control the cell cycle and can trigger programmed cell death of the damaged cell if there is a threat of cell degeneration. If the tumor suppressor genes are inactive, tumor cells can multiply unhindered.

With reduced local methylation (hypomethylation), harmful DNA elements can be activated inadvertently. If the methyl groups are incorrectly labeled, this is also referred to as epimutation. This leads to an instability of the genome.Some carcinogenic substances have been shown to interfere with the methylation process in the cells.

The changes in methylation patterns differ from cancer patient to cancer patient. For example, a patient with liver cancer has different methylation levels than a patient with prostate cancer. In this way, researchers are increasingly able to classify tumors based on their methylation pattern. The researchers can also see how far a tumor has progressed and how best to treat it. However, the analysis of DNA methylation as a diagnostic and therapeutic method is not yet fully developed, so that a few years will pass before the methods can really be used outside of the research area.

A very special disease that has its origin in methylation is ICF syndrome. There is a mutation in DNA methyltransferase, the enzyme that couples the methyl groups to the nucleotides. As a result, there is an under-methylation of the DNA in those affected. The result is recurrent infections due to an immune deficiency. In addition, short stature and failure to thrive can occur.