DNA methylation: general information

Methylation is the attachment of one carbon and three hydrogen atoms to another molecule. This phenomenon is considered the last word in the health sector. It accompanies the implementation of almost all body functions.

DNA methylation

Functions

Methyl groups (carbon and hydrogen atoms) are involved in:

  1. The body's response to stressful situations.
  2. The production and processing of glutathione. It acts as a key antioxidant in the body.
  3. Detoxification of hormones, heavy metals and chemical compounds.
  4. Monitoring inflammatory processes.
  5. Repair damaged cells.
  6. The immune response and its regulation, the fight against viruses and infections, the control of the production of T-elements.

Equally important is the process of DNA methylation . Let's consider it in more detail.

Epigenetic developmental control

DNA methylation promotes the transfer of patterns to the next generation of cells in mitosis. More recently, it was found that the process of attachment of groups of atoms in terminally differentiated structures has a definite connection with the formation of memory and synaptic plasticity. C. Miller and D. Sweet investigated DNA methylation. The study of the phenomenon led them to the conclusion that the activity of deoxyribonucleic acid methylase significantly increases in animals during the memorization of new information. This helps to reduce the expression of genes that suppress memory processes. In addition, the authors point out another phenomenon. Researchers report that memory activation affects the activation of the rilin protein gene, which promotes a change in synaptic connections and is involved in the pathological course of schizophrenia. At the same time, demitalase enzymes that provide DNA demethylation (release from methyl groups) are a determining factor. The established facts allow us to make the most important conclusion. DNA methylation as one of the epigenetic mechanisms , as well as its inverse phenomenon, play a significant role in the storage of information and memorization. This idea is confirmed by the results of a study by the E. Costa group. It was found that the demilitation of glutamate decarboxylase and rilin genes in mice can be caused by small molecules that interfere with the installation of DNA in the nucleus. These studies indicate not only the possibility of changing the prevailing notion of memory formation. They also indicate that previously considered permanent DNA methylation is dynamic. Moreover, it can be used in therapy.

DNA methylation as one of the epigenetic mechanisms

Features

The idea that memory and DNA methylation have a definite connection cannot be called a new one. The condition for synaptic transmission of histone acetylation has already been established. They form the skeleton on which DNA is wound. Acetylation leads to a decrease in the affinity of histones with nucleic acids. As a result, access is opened to DNA and other proteins, including those associated with gene activation. In fact, the histone acetyl transferase activity of CREBBP (a binding protein), which acts as a key transcription factor of neurons, has been associated with the memory's effect on this protein. In addition, a long-term memory enhancement was identified during the use of histone deacetylase inhibitors. It led to accelerated histone acetylation.

Hypotheses

Sweet and Miller asked the following question regarding histone-dependent suppression of expression of structures. If it can play a role in regulating memory, will DNA methylation have a similar effect? This phenomenon was considered mainly as a means of maintaining the activity of structures during mitosis and the formation of systems. However, in the matured mammalian brain, methylase intensity was observed, despite the fact that most of its cells are non-dividing. Due to the fact that the phenomenon under consideration contributes to the suppression of gene expression, scientists could not reject the likelihood of a connection between methylases and regulatory processes in neurons.

DNA methylation process

Checking Assumptions

Sweet and his colleagues, studying DNA methylation, the significance of this phenomenon in the formation of memory, treated hippocampal sections with deoxyribonucleic acid methyltransferase inhibitors. They found that this prevents the onset of long-term potentiation - the strengthening of synaptic connections as a reaction to neural activity. This process determines the action of learning and memory mechanisms. Scientists also found that inhibitors reduced methylation levels in rilin DNA. This indicated its reversibility.

The experiments

Deciding to go further in their studies, Sweet and Miller began to observe changes in methylation patterns in mice in a model in which animals learn to associate a specific location with unpleasant stimuli, in particular, weak shock. The behavior of test subjects treated with inhibitors expressed possible learning difficulties. Finding themselves in an environment in which they were supposed to have fear, they froze much less often than control animals.

DNA methylation study

conclusions

How could methylation affect the memory of mice? Scientists explained this as follows. In DNA, there are quite a lot of sites that can be affected by the addition of groups of hydrogen and carbon atoms. In this regard, the researchers decided to turn to the following phenomenon. They studied primarily the methylation of genes, whose role in the formation of memory has already been established. First, a plot was considered in which phosphatase protein memory processes are suppressed. Reduced expression could cause the opposite phenomenon. Indeed, after an hour of contextual conditioning of fear, the level of methylation has grown more than a hundred times. Moreover, mRNA levels in the CA1 hippocampus region underwent a weak, but statistically significant decrease. This effect is found in the brain of animals with a combination of a minor shock effect on the limbs and the novelty of the context. Separately, these stimuli do not provide any effect on methylation. Accordingly, joining groups is carried out exclusively with this training.

DNA methylation and aging

DNA methylation and aging

Problems of age and the appearance of cancer are one of the most discussed topics. For many years of research, scientists have proposed a variety of theories and models. However, not a single concept currently fully answers all the questions. Meanwhile, the study of changes in gene activity is of most interest in the search for a solution to the aging problem. In particular, Professor Anisimov expressed his opinion on this matter. It indicates that the expression (expression) of genes depends, inter alia, on methylation, which may affect the rate of aging. Up to 5% of the deoxyribonucleic acid cytosine residues underwent the addition of carbon and hydrogen atoms to form 5mC (5-methylcytosine). This base is considered the only constant in the DNA of higher organisms. Joining of groups takes place symmetrically in both threads. The remnants of 5mC are always covered by the remnants of guanine. At the same time, structures perform different functions. However, it is important to note that methylation is involved in the regulation of gene activity. Changes during the joining of groups are caused by malfunctions in the transcription level.

Causes

Age-related demethylation was first described in 1973. In this case, a difference in the degree of separation of groups in rat tissues was revealed. In the brain, demethylation was more active than in the liver. Subsequently, a decrease of 5 mC was established with age in the lungs, as well as fibroblast skin formations. Researchers have suggested that age-related demethylation determines the predisposition of cells to tumor transformation. This phenomenon can be represented in simple words as follows. An inactive gene binds to a methyl group. Under the influence of chemical reactions, it is disconnected. Accordingly, the gene is activated. A group of atoms acts as a fuse. The smaller their number, the more the cell will be differentiated and, accordingly, older, the more they will be, the younger it will be. As a classic example, widely used in the literature, the development of certain species of salmon can be cited. The phenomenon of their exceptionally rapid death immediately after spawning was revealed. Yesterday, still young individuals in reproductive age die within a short time. In biological terms, this phenomenon is accelerated aging, which is accompanied by large-scale DNA demethylation.

congenital DNA methylation

How to help the body?

There are various ways in which congenital DNA methylation can be improved. Among the most popular are:

  1. Eating fresh herbs. Leafy vegetables are especially recommended. They act as sources of folic acid necessary to ensure proper methylation.
  2. Reception of vitamins B12 and B6, riboflavin. Their sources are eggs, fish, almonds, walnuts, asparagus, etc.
  3. Reception of a sufficient amount of zinc and magnesium. They provide methylation support.
  4. Reception of probiotics. They contribute to the production and assimilation of B-group vitamins and folic acid.
    epigenetic control of DNA methylation development

It is also important to minimize stressful situations, to abandon bad habits (drinking, smoking). Care must be taken to ensure that toxic substances do not enter the body. These compounds take away methyl groups, load the liver.

Source: https://habr.com/ru/post/G11431/


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