Epigenetics

Definitions & Key takeaways

Epigenetics is the study of how environmental and lifestyle factors can change the way our genes are expressed without actually changing the DNA sequence. These epigenetic changes can be passed down from one generation to the next, which means that they can influence our health even if we don't have any direct descendants.

There are a number of different epigenetic mechanisms, but some of the most common ones include DNA methylation, histone modification, and microRNA expression. Each of these mechanisms can either promote or suppress gene expression, and they can be affected by things like diet, stress, exposure to toxins, and social interactions.

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Epigenetics is a process of gene regulation - turning genes on and off. Think about it - you have about 37 trillion cells, and over 200 different types of cells in your body.
For example, there are muscle cells, for looking great at the beach as well as neurons that tell your muscles to flex when it’s time to show off.
And both muscle cells and neurons have the same origin and genetic material - meaning, 46 chromosomes, with each chromosome made up of a single DNA molecule.
Along that chromosome are sequences of DNA that code for genes, with thousands of genes on each one. It makes sense that there would have to be a process to control all of those genes.
Now, it turns out, that DNA is a very long molecule - over 2 meters when fully stretched. So to save space, DNA is wrapped around special proteins called histones.
Now - histones actually come in groups of 8 - 4 stacks of 2, like poker chips - and the DNA molecule wraps around each group of 8 histones twice, forming a nucleosome.
Different sections of DNA - meaning, different genes - wrap around different stacks of histones. Finally, the nucleosomes are packed together even more tightly - resulting in chromatin which looks like threads of cotton-candy within the nucleus.
Now - a cell type boils down to what a cell does - and, in turn, what a cell type does boils down to the kind of proteins it makes to carry out its role.
Proteins are made based on genes - so our collection of genes, or genotype is actually like an incredible wardrobe - it contains something for every occasion.
And different cell types wear different attires. For example, our muscle cells are usually doing the hard work of contracting and relaxing all day, so they would require the equivalent of athletic gear to do their job.
Posh neurons, on the other hand, might prefer a tuxedo to tend to their synapses in. So, the muscle cell needs only certain parts of that wardrobe and the neuron needs a very different part of that wardrobe.
This is achieved through selectively activating or silencing certain genes. The final appearance of how a cell looks depends on which genes are activated - and we call that the phenotype.
All of this happens through epigenetics - which specifically refers to mechanisms that can selectively activate or silence certain genes without modifying the nucleotide sequence of the gene.
Let’s start with histones. Histones can be influenced to either release their DNA or lock down their DNA, through chemical changes, like acetylation or methylation.
For example, when an acetyl group is added to the histone, there’s less attraction between DNA and histones. As a result, the genes are more exposed and therefore more easily transcribed.
Removing the acetyl group through deacetylation has the opposite effect - DNA wraps tighter around the histones, so the genes are less easily transcribed.
Methylation, on the other hand can both increase and decrease transcription, depending on how many methyl groups are added.
If only one methyl group is added to the histone, this decreases the attraction between the DNA and the histone, so the genes are easily accessible.
But interestingly, if two or three methyl groups to the histone, the histone will repress, or lock down the DNA, preventing the transcription of those genes.
Epigenetics can also include a direct modification of the DNA, in a way that doesn’t change its nucleotide order. Genes are just a particular sequence of the 4 nucleotides - adenine, or A, thymine, or T, guanine, or G and cytosine - or C.
These four bind to each other specifically - A on one strand binds with the T on the other, while the C pairs with G, and vice versa.
Epigenetic modifications usually occur in regions of DNA that have a lot of cytosine and guanine nucleotides one after the other; and these regions are called CpG sites.
In these regions, the cytosine residues can be undergo methylation - so a methyl group is now hanging off the cytosine, but the sequence of nucleotides remains unchanged.
A lot of DNA methylation can silence gene expression, so if a gene contains many methylated cytosines, it will be less likely to get expressed.
You can think of methylated cytosines in DNA as thorns on a rose stalk - making that rose less likely to be picked. It’s also important to remember that rather than being an on/off switch these epigenetic modifications just help to tune the frequency of something happening - like a dimmer switch.
So if someone is truly after that rose - it might still get picked, albeit with some pain. Now the key is that epigenetic modifications on both histones and DNA can occur throughout a person’s lifetime - from fetal development through the aging process, and various factors like recreational drugs, medications, diet, and exercise can all play a role.
Many epigenetic changes are reversible - so changing these factors can affect these epigenetic modifications and gene expression.
In fact, epigenetics help explain why identical twins have the same DNA but often have subtle differences in their appearance, their personality, and even in the diseases that they might develop.
Epigenetic changes are also potentially heritable, but how chemical modifications of DNA get inherited is still an area of intense research.
Alright, as a quick recap: epigenetics refers to the chemical modifications that can selectively activate or silence certain genes without modifying the nucleotide sequence of the gene.
For histones, this can happen through acetylation which activates gene expression, deacetylation which deactivates gene expression, or methylation which can do both.
Finally, DNA can be epigenetically altered by methylation of a cytosine residue in a CpG site, which silences gene expression.