- Epigenetics - what are epigenetic modifications?
- Epigenetics - types of epigenetic modification
- Epigenetics - the role of epigenetic modifications
- Epigenetics - diet
- Epigenetics - MTHFR gene polymorphisms
- Epigenetics - stress
- Epigenetics - impact on he alth
Help the development of the site, sharing the article with friends!VERIFIED CONTENTAuthor: Karolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, nutrition and lifestyle consultant
Can Diet Change Our Genes? Could Our Childhood Traumas Affect Our Children and Grandchildren? Answers to these questions can be provided by epigenetics, i.e. the science that studies the so-called epigenetic modifications. Currently, epigenetic modifications are considered to be one of the most important discoveries in molecular biology, as they allowed the understanding of the relationship between the genetic background and environmental factors.
Epigeneticsis a branch of science that studies changes in gene expression that do not result from sequence modifications in a DNA strand. Such modifications are called epigenetic and they are a type of molecular markers that are added to DNA strands by appropriate enzymes, e.g. methyltransferases.
By means of epigenetic modifications, the body can control the course of many key biological processes, such as the development of individual tissues and organs in the uterus.
The term "epigenetics" was first used by Waddington in 1942. The prefix "epi-" comes from the Greek word "above", which loosely translated means something that is above classical genetics.
Epigenetics - what are epigenetic modifications?
Molecular markers added to a DNA strand during epigenetic modifications can determine whether or not a gene is expressed, acting as molecular "switches" and "switches" that regulate the expression of particular genes.
Most importantly, these types of modifications do not change the structure of the DNA strand, i.e. they are not a type of genetic mutation that is irreversible, but something that undergoes dynamic changes under the influence of environmental factors.
In addition, appropriate molecular markers are added or removed after each cell division and DNA strand duplication.
Hence, each cell has its own characteristic pattern of molecular markers, which determines its specific gene expression profile. The collection of such molecular markers isepigenom .
The best known epigenetic modification isDNA methylation , which involvesattaching a methyl group to cytosine (a basic compound that is part of DNA).
The reverse epigenetic modification to methylation isdemethylation , which consists in removing the methyl group from cytosine.
Epigenetics - types of epigenetic modification
Epigenetic modifications can directly affect the DNA strand:
- DNA methylation, i.e. joining methyl groups to cytosine by means of DNA methyltransferases
- DNA demethylation, i.e. the separation of cytosine methyl groups by means of DNA demethylases
- In addition, epigenetic modifications are made of proteins on which nothing DNA is wound, i.e. histones:
- methylation of lysine and arginine residues of histones with histone methyltransferases
- demethylation of lysine and arginine residues of histones with histone demethylases
- acetylation of histone lysine residues with histone acetyltransferases
- deacetylation of histone lysine residues with histone deacetylase
- phosphorylation of histone serine residues by kinases
- ubiquitination of histone lysine residues by attaching ubiquitin protein to histones using the enzymes E1, E2 and E3
- ribosylation of histone glutamine and arginine residues involving the attachment of ADP-ribose nucleotides using polymerase and transferase
Atypical epigenetic modification are the so-called non-coding RNA molecules e.g. microRNA (miRNA). They are short, single-stranded RNA molecules (DNA-like compounds) that can regulate gene expression by blocking the formation of proteins.
Epigenetics - the role of epigenetic modifications
- enhanced gene expression
- silencing gene expression
- control of cell differentiation in the body
- embryonic development
- regulation of the degree of chromatin condensation, e.g. inactivation of the X chromosome, thanks to which only one copy of sex-linked genes is active in women.
An interesting example of the role of epigenetic modifications in animal development is bees. In these insects, the queen is the mother of all bees in one hive, with the consequence that they all have the same DNA sequence.
Despite this, one hive is inhabited by insects that look and behave in a different way. The workers are smaller than the queen and have a mild temper, while the soldiers are larger and aggressive.
These differences are caused by epigenetic modifications that determine the appearance and behavior of bees adapted to the role they play in the hive community.
A similar mechanism is observed during developmentfetal animals, when silencing and enhancing the expression of specific genes affects the fate of a given stem cell, whether it will be a nerve cell of the brain or an epithelial cell of the stomach.
Epigenetics - diet
Epigenetic modifications occur during fetal life and can then undergo dynamic changes throughout life under the influence of environmental factors.
One of the most important factors influencing the shape of the epigenome is food and its bioactive substances.
The influence of diet on epigenetic modification has been confirmed in many preclinical and clinical studies.
There are at least two mechanisms by which diet may affect epigenetic modification, mainly the methylation process:
- by changing the availability of methyl donors such as S-adenosylmethionine (SAM), which is synthesized in the methionine cycle from several precursors present in food, including methionine, choline and its derivative betaine, folic acid and vitamins B2, B6 and B12 . Therefore, the reduced availability of these compounds may result in reduced SAM synthesis and disturbances in the methylation process
- by modulating the activity of enzymes related to the methylation process (e.g. DNMT methyltransferase) through the consumption of polyphenols contained in fruits, vegetables and spices. Examples of such compounds are resveratrol in red wine, epigallocatechin gallate (EGCG) in green tea, curcumin in turmeric rhizome, genistein in soybeans, sulforaphane in broccoli, quercetin in citrus fruits and buckwheat
The influence of diet on the epigenome in utero was documented by the famous experiment on "agouti" laboratory mice, which are characterized by a yellow coat color and a predisposition to obesity, diabetes and cancer.
The yellow color of the fur in these mice is a kind of indicator of insufficient gene methylation.
In the experiment, pregnant "agouti" mice were fed food with a high content of methyl donors, among others. folic acid and choline.
To the scientists' surprise, the offspring of these mice did not resemble their parents. The first noticeable trait was the change in coat color to brown, but the most surprising thing was that the mice lost their predisposition to diseases that their parents suffered from.
As it turned out, it was a consequence of a modified diet and restoration of proper DNA methylation.
These observations support the fact that the epigenome can be altered through diet and can have far-reaching he alth consequences.
In the lastover the years, a significant role of the gut microbiota in the process of epigenetic modification has also been demonstrated.
The intestinal microorganisms produce various bioactive substances, e.g. short-chain fatty acids, and their amount depends on the species composition of the microbiota and the quality of the diet.
A high supply of prebiotic products in the diet, such as soluble dietary fiber, e.g. resistant starch, increases the concentration of short-chain fatty acids, which positively affect the epigenome of intestinal epithelial cells.
Epigenetics - MTHFR gene polymorphisms
The efficiency of epigenetic modifications may also be influenced by genetic polymorphisms, i.e. small changes in the genome, the consequence of which is the presence of different gene variants in the human population.
One of the consequences of genetic polymorphisms is, among others. everyone's different response to nutrients.
It is estimated that 15-30% of people may have an increased need for methyl donors (especially folic acid) due to unfavorable polymorphisms of the MTHFR gene, which encodes the enzyme methylenetetrahydrofolate reductase.
This enzyme is responsible for converting folic acid into its active form.
People with an unfavorable variant of the MTHFR gene polymorphism have impaired conversion of the inactive form of folic acid to its active form 5-methyltetrahydrofolate (5-MTHF), hence they have an increased need for methyl donors.
And although studies have not unequivocally confirmed that such people may have reduced DNA strand methylation, in their case it is worth paying attention to an adequate supply in the diet or additional supplementation of methyl donors, such as folic acid or choline.
Epigenetics - stress
Excess of stress hormones, incl. cortisol may affect epigenetic modifications in the nervous system and increase the risk of psychiatric disorders.
It has been documented that people suffering from anxiety disorders, post-traumatic stress disorder, post-traumatic stress disorder and depression have a characteristic epigenetic modification profile (mainly decreased DNA methylation).
They are believed to develop such epigenome as a result of childhood traumatic experiences and / or chronic stressful situations.
This epigenetic profile is maintained in them throughout their lives and is probably passed on to children and grandchildren (known as extragenic inheritance).
Epigenetics - impact on he alth
Errors during epigenetic modifications, such as silencing the expression of a wrong gene, can have serious consequences in the functioning oforganism, e.g. cause cancer.
In addition, more and more studies indicate that epigenetic modifications, in addition to participating in physiological processes, may participate in the development of diseases such as:
- cardiovascular diseases
- neurodegenerative diseases
- autoimmune diseases
The relationship between epigenetic modifications, diet and the risk of certain diseases is being especially sought.
It has been shown that significant epigenetic modifications occur in utero, which may have implications in adulthood.
Therefore, what the mother eats during pregnancy may increase the risk of certain diseases and even affect the next generation.
It has been proven that children of mothers who were pregnant during the hunger winter in the Netherlands of 1944-1945 had an increased risk of cardiovascular disease, obesity and schizophrenia compared to children of mothers who did not starve.
In children of hungry mothers it was found, among others, reduced methylation of the gene encoding insulin-like growth factor 2 (IGF2).Worth knowing
The advancements of epigenetics are currently the subject of intense research in nutritional science. There is even a new discipline dealing with the influence of nutrients on gene expression, i.e.nutrigenomics .About the authorKarolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, Cambridge Diagnostics Polska A biologist by profession, specializing in microbiology, and a laboratory diagnostician with over 10 years of experience in laboratory work. A graduate of the College of Molecular Medicine and a member of the Polish Society of Human Genetics. Head of research grants at the Laboratory of Molecular Diagnostics at the Department of Hematology, Oncology and Internal Diseases of the Medical University of Warsaw. She defended the title of doctor of medical sciences in the field of medical biology at the 1st Faculty of Medicine of the Medical University of Warsaw. Author of many scientific and popular science works in the field of laboratory diagnostics, molecular biology and nutrition. On a daily basis, as a specialist in the field of laboratory diagnostics, he runs the content department at Cambridge Diagnostics Polska and cooperates with a team of nutritionists at the CD Dietary Clinic. He shares his practical knowledge on diagnostics and diet therapy of diseases with specialists at conferences, training sessions, and in magazines and websites. She is particularly interested in the influence of modern lifestyle on molecular processes in the body.
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