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

So how can they act any differently? In other words, how can a neuron be a neuron and not a hepatocyte if they have the same DNA? The answer is in epigenetics .

What is epigenetics?

Although it contains the information, the deoxyribonucleic acid chain is not the whole story, as there is an important component which is the environment. This is where the term epigenetics comes in, “about genetics” or “in addition to genetics”.

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

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

A simple way to understand epigenesis was given to me by a good friend with this example: if we think that DNA is 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 the 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. Depending on the type of cell it is, at what stage of development the organism is, or even the very environment where the individual lives, there will be some genes that are active and others that are not. The presence of a group of proteins that are responsible for controlling gene expression without modifying the DNA sequence, i.e. without causing mutations or translocations, for example, allows this.

Knowing the epigenome

The concept of epigenome was born as a consequence of the emergence of epigenetics, and it is just all the components that are part of this regulation of gene expression.

Unlike the genome, which remains stable and unchanged from birth to old age (or should be), the epigenome is dynamic and variable. Throughout development it changes, can be affected by the environment , and is not the same according to the type of cell. To put an environmental effect into perspective, it has been seen that tobacco use has a negative impact on the epigenome, which favours the appearance of cancer.

Before we continue, it is useful to take a brief look at genetics to understand the purpose of DNA. The genetic code contains genes, but for that very reason this would have no consequences. In general, 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 only consists of the fragment of the read gene.

This RNA obtained must be 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 RNAm. Having a clear idea of how this 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 has found a method to drastically reduce the size and package it inside the nucleus of the cell: thanks to structural proteins called “histones” , which are grouped in groups of eight to form the nucleosome, they support the DNA chain to be wound on it 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 folding makes it difficult for RNA polymerase to read the genes, so it is not always found folded in the same way in different cells. By not allowing access to RNA polymerase, it is already exerting control over gene expression without modifying the sequence.

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

Is the epigenome inherited?

The genome, which is invariable, is inherited from each of an individual’s parents. But does the same thing happen with the epigenome? This subject has brought much controversy and doubt.

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

The main problem with this type of study is that it does not describe the process, but is only guesswork without a demonstration to resolve the doubt.

As for those who believe that the epigenome is not inherited, they rely on a study that reveals a family of genes whose main function is 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 can be the way to investigate and understand vital processes 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 drug therapies to fight this disease.

Aging

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

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 ageing there are changes again, but this time downwards rather than upwards.

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

As an application for the understanding of 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 using this pattern one could 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 original tissue 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 cancerous by affecting gene expression.

In the DNA there are genes known as “cancer suppressors” ; their very name indicates what their function is. Well, in some cases of cancer it has been seen that these genes are methylated so that they inactivate the gene.

Currently, we are looking to study whether epigenetics affects other types of pathologies. There is evidence to suggest that it is also involved in atherosclerosis and 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 in some types of cancer , mainly leukaemia and lymphoma, where the drug aims at DNA methylation.

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

However, the biggest challenge is to obtain all the information on the human epigenome, in the form of sequencing of the human genome. With more extensive knowledge, in the future more personalized and individualized treatments could be devised, by being able to know the needs of the cells in the damaged area in a specific patient.

Science needs more time

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

What must be clear is that epigenetics 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.