General and Definition
Epigenetics deals with the study of all those heritable modifications that lead to variations in gene expression without however altering the DNA sequence, and therefore without causing modifications in the sequence of the nucleotides that compose it.
Using a more technical language, however, we can affirm that epigenetics studies all those modifications and all those changes that are able to vary the phenotype of an individual, without however altering the genotype.
The merit of "having coined the term" epigenetics "is attributed to the biologist Conrad Hal Waddington who, in 1942, defined it as" the branch of biology that studies the causal interactions between genes and their product, and brings about the phenotype ".
Explained in these terms, epigenetics may seem rather complex; to better understand the concept it may be useful to open a little parenthesis on how DNA is made and how the transcription of the genes it contains takes place.
DNA and Gene Transcription
DNA is contained within the cell nucleus. It has a double helix structure and is made up of repetitive units, called nucleotides.
Most of the DNA contained within our cells is organized in particular subunits called nucleosomes.
Nucleosomes are made up of a central part (called core) made up of proteins called histones around which DNA wraps.
The set of DNA and histones constitutes the so-called chromatin.
The transcription of the genes contained in the DNA depends precisely on the "packaging of the latter" inside the nucleosomes. In fact, the gene transcription process is regulated by transcription factors, particular proteins that bind to specific regulatory sequences present on the DNA and which are able to activate or repress - depending on the case - specific genes.
DNA with a low level of packing will therefore allow transcription factors to access the regulatory sequences. Conversely, DNA with a high level of packing will not allow them access.
The level of packing is determined by the histones themselves and the changes that can be made in their chemical structure.
More specifically, the "acetylation of histones (ie the addition of an acetyl group at particular sites on the amino acids that make up these proteins) causes the chromatin to assume a" more relaxed "conformation allowing the entry of transcription factors , hence gene transcription. On the other hand, deacetylation removes acetyl groups, causing the chromatin to thicken and thus blocking gene transcription.
Epigenetic signals
In the light of what has been said so far, we can affirm that, if epigenetics studies the modifications capable of changing the phenotype, but not the genotype of an individual, an epigenetic signal is that modification capable of altering the expression of a given gene, without altering the nucleotide sequence.
Consequently, we can affirm that the acetylation of histones mentioned in the previous paragraph can be considered as an epigenetic signal; in other words, it is an epigenetic modification capable of influencing the activity of the gene (which can be transcribed or less) without altering its structure.
Another type of epigenetic modification is constituted by the methylation reaction, both of the DNA and of the histones themselves.
For example, the methylation (ie the addition of a methyl group) of DNA at a promoter site reduces the transcription of the gene, whose activation is regulated by that promoter site itself. In fact, the promoter site is a specific sequence of DNA located upstream of the genes, whose task is to allow the transcription of the same to begin. The addition of a methyl group at this site therefore causes a sort of encumbrance which hinders gene transcription.
Still, other examples of currently known epigenetic modifications are phosphorylation and ubiquitination.
All these processes involving DNA and histone proteins (but not only) are regulated by other proteins that are synthesized following the transcription of other genes, whose activity can, in turn, be altered.
In any case, the most interesting peculiarity of an epigenetic modification is that it can take place in response to external environmental stimuli that concern, precisely, the environment that surrounds us, our lifestyle (including nutrition) and our health state.
In a sense, an epigenetic modification can be understood as an adaptive change operated by the cells.
These changes can be physiological, as happens in the case of neurons that adopt epigenetic mechanisms for learning and memory, but they can also be pathological, as happens, for example, in the case of mental disorders or tumors.
Other important characteristics of epigenetic modifications are reversibility and heredity. In fact, these modifications can be transmitted from one cell to another, although they can still undergo further changes over time, always in response to external stimuli.
Finally, epigenetic modifications can occur in different phases of life and not only at the embryonic level (when the cells differentiate) as was once believed, but also when the organism is already developed.
Therapeutic Aspects
The discovery of epigenetics and epigenetic modifications can be widely exploited in the therapeutic field for the potential treatment of different types of pathologies, including those of the neoplastic type (tumors).
In fact, as mentioned, the epigenetic modifications can also be of a pathological nature; therefore, in these cases, they can be defined as real anomalies.
The researchers therefore hypothesized that, if these changes can be influenced by external stimuli and can manifest themselves and further modify themselves throughout the life of the organism, then it is possible to intervene on them using specific molecules with the aim of bringing the situation back to normal conditions. of normality. This is something that cannot be done (at least not yet) when the cause of the disease lies in a real genetic mutation.
To better understand this concept we can take as an example the use that researchers have made of the knowledge of epigenetics in the field of anticancer therapies.
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