What is epigenetics? Keys to understanding it

We describe the main concepts and therapeutic applications of this booming science.

How important is DNA. The genetic code is the key piece of life.In the case of humans, it stores the information that allows the organism to develop from among the 20,000 genes that make up the genome. All the cells of the same body have the same DNA.

So how is it possible for them to act differently? Or rather, how is a neuron a neuron and not a hepatocyte, if they have the same DNA? The answer lies in epigenetics.

What is epigenetics?

Although it contains the information, the deoxyribonucleic acid chain is not everything, since there is an important component which is the environment. This is where the term epigenetics, "over genetics" or "in addition to genetics" comes in.

There are factors external to the genetic code that regulate the expression of the different genes, but always the expression of the different genes, but always keeping the DNA sequence intact. It is a mechanism that has its relevance: if all genes were active at the same time it would not be any good, so control over expression is necessary.

The term epigenetics was coined by the Scottish geneticist Conrad Hal Waddington in 1942 to refer to the study of the relationship between genes and environment. study of the relationship between genes and environment.

A simple way to understand epigenesis was given to me by a good friend with this example: if we think of DNA as a library, genes are the books and gene expression is the librarian. But the libraries themselves, the dust, the shelves, the fires... anything that prevents or helps the librarian from being able to access the books would be epigenetics.

The reality is that the human genome consists of more than 20,000 genes, but these are not always active at the same time.but these are not always active at the same time. Depending on the type of cell, the stage of development of the organism or even the environment in which the individual lives, some genes will be active and others not. The presence of a group of proteins that is responsible for controlling gene expression without modifying the DNA sequence, i.e. without causing mutations or translocations, for example, makes this possible.

Understanding the epigenome

The concept of epigenome was born as a consequence of the emergence of epigenetics, and is nothing more than all the components that are part of this regulation of gene expression.

Unlike the genome, which remains stable and immutable from birth to old age (or so it should be), the epigenome is dynamic and variable. Throughout development it changes, can be affected by the environmentand it is not the same depending on the type of cell. To give an environmental effect, it has been shown that tobacco consumption has a negative impact on the epigenome, which favors the appearance of cancer.

Before continuing, a brief review of genetics is in order to understand the purpose of DNA. The genetic code contains genes, but this alone would have no consequences. Generally speaking, it is necessary for a protein complex called RNA polymerase to "read" this gene and transcribe it into another type of nucleic acid chain called "messenger RNA" (mRNA), which consists only of the fragment of the gene read.

It is necessary that this RNA obtained is translated into the final product, which is none other than a protein, formed by another molecular complex known as ribosome, which synthesizes the protein from the mRNA. Having clarified how it works, I continue.

Epigenetic mechanisms

DNA is a very large structure, which in the case of humans is almost two meters long, much larger than the diameter of any cell.

Nature is wise and found a method to drastically reduce the size and pack it inside the cell nucleus: thanks to structural proteins called "histoneswhich are grouped in groups of eight to form the nucleosome, they support the DNA strand so that it can be coiled into the nucleosome and facilitate folding.

The DNA strand does not compact completely, leaving more free parts for the cell to carry out its functions. The truth is that the folding makes it difficult for RNA polymerase to read the genes, which is why it is not always folded in the same way in different cells. By not allowing access to RNA polymerase, it is already exerting control over gene expression. exerting control over gene expression without modifying the sequence. without modifying the sequence.

It would be very simple if it were only this, but the epigenome also makes use of chemical markers. also makes use of chemical markers. The best known is DNA methylation, which consists of the attachment of a methyl group (-CH3) to deoxyribonucleic acid. This marker, depending on its placement, can both stimulate the reading of a gene and prevent it from being reached by RNA polymerase.

Is the epigenome inherited?

No. The genome, which is invariable, is inherited from each of an individual's parents. But is the same true for the epigenome? This subject has been the subject of much controversy and doubt.

Remember that, unlike the genetic code, the epigenome is dynamic. There are scientific groups that are convinced that it is also inherited, and the most common example they give is a case of a village in Sweden where the grandchildren of grandparents who suffered famine live longer, as if it were a consequence of epigenetics.

The main problem with this type of studies is that they do not describe the process, but are only conjectures without a demonstration that resolves the doubt.

As for those who believe that the epigenome is not inherited, they base their opinion on a study that reveals a family of genes whose main function is to to restart the epigenome in the zygote.. However, the same study makes it clear that the epigenome is not completely restarted, but that 5% of genes escape this process, leaving a small door open.

The importance of epigenetics

The importance that is being given to the study of epigenetics is that it may be the pathway to to investigate and understand vital processes such as aging, mental such as aging, mental processes or stem cells.

The field in which most results are being obtained is in the understanding of Cancer biology, looking for targets to generate new pharmacological therapies to fight this disease.

Aging

As mentioned earlier in the text, the epigenome in each cell changes according to the stage of development a person is in.

There are studies that have proven this. For example, it has been observed that the genome varies in the human brain from birth to maturity, while in adulthood until well into old age it remains stable. During aging there are changes again, but this time downward instead of upward.

For this study they focused on DNA methylations, finding that they were generated more during adolescence and decreased in old age. In this case, the lack of methylation hinders the work of RNA polymerase, leading to a decrease in DNA methylation.which leads to a decrease in efficiency on the part of the neurons.

As an application for understanding aging, there is a study that makes use of DNA methylation patterns in bloodline cells as indicators of biological age. Sometimes, chronological age does not coincide with biological age, and with the use of this pattern it would be possible to know the health status and mortality of the patient in a more concrete way.

Cancer and pathologies

Cancer consists of a cell that for some reason ceases to be specialized in its tissue of origin and begins to behave as if it were an undifferentiated cell, without limiting its proliferation or moving to other tissues.

Logically, it is normal to think that changes in the epigenome can cause a cell to become can cause a cell to become cancerous by affecting gene expression. by affecting gene expression.

There are genes in the DNA that are known as "suppressor" genes. genes that are known as "cancer suppressors"; the very nameTheir very name indicates their function. Well, in some cases of cancer it has been seen that these genes are methylated in such a way that they inactivate the gene.

We are currently studying whether epigenetics affects other types of pathologies. There is evidence to suggest that it is also involved in arteriosclerosis and in some types of mental illness.

Medical applications

The pharmaceutical industry has its sights set on the epigenome, which, thanks to its dynamism, is a feasible target for future therapies. Treatments are already being put into practice treatments are already being put into practice for some types of cancer, mainly leukemiasmainly in leukemias and lymphomas, where the drug targets DNA methylation.

It should be noted that this is effective as long as the origin of the cancer is epigenetic and not another, such as a mutation.

However, the greatest challenge is to obtain all the information on the human epigenome, in the manner of human genome sequencing. With a broader understanding, more personalized treatments could be devised in the future more personalized and individualized treatments could be devised and individualized treatments could be devised in the future by knowing the needs of the cells in the damaged area in a particular patient.

Science needs more time

Epigenetics is a fairly new field of research and further study is needed to understand the subject.

What needs to be clear is that epigenetics is all about consists of regulations of gene expression that do not modify the DNA sequence. It is not uncommon to find erroneous mentions of epigenetics in cases of mutations, for example.