A liberating science?

When people say epigenetics is liberating, they’re probably thinking of certain views that have been put forward saying there’s life after DNA, or DNA is not your destiny. It’s quite a strong statement. But epigenetics is not so recent. The term was coined by Conrad Waddington in the 1940s – a lot earlier than when we learned about the structure of DNA, which came about in 1953.

DNA testing in a scientific laboratory. By Sergei Drozd.

Epigenetics is a clever way of putting together two words: epigenesis and genetics. Epigenesis was first used by Aristotle to designate how a whole organism can develop from an unformed state to complexity. The idea to combine it with genetics was to show that there’s an aspect of heredity that will be shaped and can change depending on the environment.

So this was meant to explain how – with the same genetic material – one cell, the egg, can give rise to the many cells that build up our body. How do you make cells for your eye; how do you make cells for muscles; how do you make cells that are critical for your heart? All of these cells basically have the same genetic material, yet they use it in a different manner. One thing we would like to understand is this capacity to give rise to different cells. But another important aspect is that when these cells engage in a lineage, they keep this memory and act the same way.

Epigenetics and genetics

In order to explain the tight connection between genetics and epigenetics, it’s important to remember that more than DNA is involved. DNA is the molecular material that carries information of a genetic nature, but there are other factors that may also be inherited. In a way, genetics and epigenetics are like Russian dolls, intertwined. It’s hard to totally disconnect them and say, ‘Genetics is everything that is in your DNA, and it’s completely unchangeable and you have it forever, and epigenetics is superimposed on top.’ They are more related than one might think.

Then we can take the historical intersection of epigenetics and genetics. The discovery of DNA was a turning point. Suddenly there was some molecular understanding of the material underlying inheritance. This didn’t mean that everything else was in conflict; epigenetics provided an explanation of changes we did not understand, which went beyond the molecular structure of DNA.

Epigenetics came about again with regard to the methylation of DNA. In that case, it was not the DNA itself but its methylation that could bring an additional piece of information that could also be inherited. So that was a version of epigenetics that evolved with Robin Holliday in particular. Since then, epigenetics has continued to develop through research. This is the beauty of the term – it has an evolving meaning.

Explaining the inexplicable

Some aspects that epigenetics tried to explain were related to particular features of colours in flowers. These features did not appear to obey Mendel’s laws of inheritance. When considering characteristics that were not inherited according to the laws of formal genetics, something else needed to be imagined, and that’s where epigenetics came in. The cause of these features could be related to many factors, and epigenetics started to provide an explanation for the inexplicable. Since the research has progressed, more and more possibilities have come about to give ideas of what could convey this capacity to inherit traits that are not directly encoded in DNA and inherited according to Mendelian laws.

DNA is definitely a very important part of all of us, and we wouldn’t be here without it, but it doesn’t explain everything. You have different types of cells that have the same DNA, and they express different genes to give rise to different proteins and different characteristics.

There is a way to read DNA, and the cells are these entities that can read DNA and make sense of it. It’s as if you have a book. If you don’t know how to read it, it’s nice to have; you put it on your shelf, but you don’t do anything with it. But if you learn to read, you can choose the chapter that you want to read, and you can go into particular stories. This is what our cells are doing, which allows the whole body to function.

Scientists examined DNA by Gopixa

Posing research questions

In the discovery process, when you are driven to understand the mechanism behind epigenetics, you start by formulating your questions. For example, how is a particular property inherited through multiple cellular divisions without necessarily involving something encoded within the DNA sequence? That would be one way to phrase the problem.

Then it boils down to your particular question in your lab. In my lab, we have been interested in the way that DNA is organised in the chromatin of each cell, and how this organisation can regulate gene expression. How does it work with the transcriptional machinery? How does it work with the replication machinery and with the cell cycle when the chromosomes undergo segregation? So we have been looking at this very fundamental break that is the nucleosome, the basic unit of chromatin.

The issue of epigenetics with transgenerational transmission is definitely the most challenging one. It’s not simple to address, at least at the level of the human population, because you will have to work on a very large range of people. But there are studies that have been carried out with twins to try to resolve this question.

With model organisms, small worms for example, it has been possible to try and follow some traits or some marks at the chromatin level that could be transmitted through generations. In plants, people have also been working quite extensively in trying to understand what kind of methylation pattern, for example, could be inherited or reversed and passed down through multiple generations. Studying this requires a very careful population analysis, so it’s not simple.

Epigenetics and healthcare

To consider how epigenetics has helped from a medical point of view, it helps to translate the term epigenetics to epigenomics. With the term epigenetics, you can go quite far in covering a broad range of possibilities. With epigenomics, you define things that are related to how the genome, your DNA, is modified or changed by interacting with proteins – proteins that can be modified or modify themselves. You look at how much of this can be inherited, and how this can be reversed.

If you have a defect in a disease context that is not in your DNA and that is potentially reversible, then with the proper drugs or tools to reverse it, you have a chance to get back to normal. That has really stimulated a lot of development for pharmaceutical approaches in the context of cancer, for example, as well as for neurological diseases and many other diseases where the problems encountered could be related to this level.

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Jeffery, D., Gatto, A., Podsypanina, K., et al. (2021). CENP-A overexpression promotes distinct fates in human cells, depending on p53 status. Communications Biology, 4, 417.

Torné, J., Ray-Gallet, D., Boyarchuk, E., et al. (2020). Two HIRA-dependent pathways mediate H3.3 de novo deposition and recycling during transcription. Nature Structural & Molecular Biology, 27, 1057–1068.

Going beyond DNA: the science of epigenetics