Epigenetics and the influence of our genes | Courtney Griffins | TEDxOU

Transcriber: H Maria Castro Reviewer: Denise RQ Nine years ago, I found myself in a doctor's office, contemplating the nature-nurture debate from a new perspective. You see, I had trained as a geneticist and had spent my career manipulating DNA and seeing the profound consequences in a laboratory, so I had always put my money more on the nature or genetic side of the debate. But, when my doctor revealed to me that she was pregnant with identical twins, I realized that my beliefs were about to be tested. To begin with, we hadn't budgeted for two daycare bills at once.

So, half-jokingly, I began to wonder what the consequences would be if we sent one twin to daycare and perhaps kept the other in my office drawer during the work day. (Laughs) Despite his identical DNA, I somehow doubted things would turn out so well for the twin in the office drawer. (Laughter) Identical twins have had a profound impact on scientists' understanding of nature and nurture. Studies on identical twins who were separated at birth and raised in separate homes have helped us understand different traits that are more affected by nature, or DNA, than by nurture or home environment.

For example, some traits, like IQ or criminal tendencies, are more affected by your DNA than the house you grew up in. On the other hand, other traits, such as depression in men or your preference for a particular political party, are more

influence

d by your environment than by your

genes

. What about identical twins who grow up in the same family environment? Their nature and breeding are almost the same. And yet, any parent of identical twins, myself included, can quickly point out the differences in their children. One twin may have more preferences for certain types of foods or may have more aptitude for a certain sport or musical instrument.

And sometimes health differences can arise in these children. For example, there are reports of autism, asthma, or bipolar disorder emerging in one twin at a young age while the other is unaffected. How do we explain these differences, given that the DNA is the same in these children? And, to a large extent, the family environment has also been the same. Well, it turns out that some of these differences can be explained by a third, very powerful

influence

in our lives, besides nature and nurture. This is

epigenetics

. Today I'm going to talk to you about what

epigenetics

is and how it impacts your life, even if you are not an identical twin.

Before we talk about epigenetics, we need to consider our DNA and how it fits into our cells because, believe it or not, of the approximately 50 trillion cells in your body, each one contains about six linear feet of DNA. If we extended it, it would be as tall as a fairly tall man. So how can we fit that amount of genetic material into something the size of a cell nucleus, which is 400,000 times smaller? Well, the answer is that we do this by wrapping our DNA around clumps of proteins called histones. You can think of histones as molecular reels.

There are about 30 million of these reels in each of its cells. This helps explain how such a huge amount of DNA fits into a small space. We call this combination of histones and DNA chromatin. While chromatin solves this tremendous packaging problem that the cell has, it also presents a new one for the cell. This is a question of DNA accessibility because it must be taken into account that the functional units of DNA are actually the

genes

encoded in it. These are the instructions for the cell phone. There are things that tell the cell what to do and who to become, and yet when these genes are tightly packed into a chromatin structure, the cell cannot read them and they may not even be there.

This is where epigenetics comes into play. “Epi” means “on top of,” and “genetics,” its “genes,” literally refers to a set of instructions that sit on top of our DNA and histones. Epigenetic marks are small chemical tags that are deposited on our chromatin and can help tell it whether it should be compacted or decompacted. Those instructions can then affect how the cell reads the underlying genes encoded in the DNA. So, to show this schematically, some epigenetic marks, shown here in red, can help condense chromatin. When they do this, they obscure the underlying genes, preventing the cell from reading them.

They deactivate those genes. Other epigenetic marks, shown here in green, can help decondense chromatin. When they do this, the gene becomes accessible to the cell, the cell can read it and activate it. These types of epigenetic marks have a profound influence on our biology. Consider, for example, what makes our cells different from each other, what makes them look and behave differently, what makes a muscle cell, for example, look different from a muscle cell? neuron? After all, these cells contain the exact same DNA, but it is their epigenetic instructions that help them tell which genes to turn on and which to turn off.

With those different genes in play, these can become very different cells. You may be wondering when all this epigenetic information is deposited into our chromatin. The answer is that much of this occurs during our embryonic development. Interestingly, when you were first conceived and were only composed of a few undifferentiated embryonic stem cells, which had the potential to become any cell in your body, your chromatin did not have many epigenetic marks. It was only when its cells began to divide and receive signals and information from surrounding cells, that epigenetic marks began to accumulate and then genes began to turn off and on, and the muscle cell became very different from the neuron.

This brings me to a really important point about epigenetics. Epigenetic marks can be influenced by the environment. When I say environment, I don't just mean the surrounding cells that tell a neuron to become a neuron. I am also referring to the external environment of the developing embryo. Thus, the food the mother eats, the prenatal vitamins she takes, the cigarettes she smokes, or the stress she faces at home or at work can be transmitted as chemical signals through the bloodstream to her developing mother. fetus, where they can be established as epigenetic marks that affect the fetus's own genes and its long-term health.

This has been demonstrated experimentally in mice. Mice contain a gene called agouti, which makes them obese, yellow and susceptible to diseases such as cancer and diabetes. This gene and these traits can be passed from generation to generation through DNA, so that an agouti mother will give rise to offspring that are fat, yellow, and susceptible to disease, if those offspring contain the agouti gene. Here's something interesting about the agouti gene. It can be deactivated if silencing epigenetic marks accumulate around it. So, if a pregnant agouti mother receives a diet supplemented with these silencing epigenetic marks, those marks will be chemically transmitted to the DNA of her embryo, where they will accumulate around that agouti gene and effectively turn it off.

Her embryo will keep those marks. Then she will be born and grow into a thin, brown, healthy adult mouse. Although this mother is genetically identical at the DNA level to both sets of offspring, it can be seen that the diet she consumed during pregnancy can affect the health and appearance of her offspring. This, of course, has implications beyond the world of mice, because human studies have shown that women who do not eat well during pregnancy, who eat bad foods, will have children who are more susceptible to developing obesity and cardiovascular problems. disease. Likewise, if women smoke during pregnancy, their children will grow older and have a greater chance of developing asthma.

These correlations between maternal behavior during pregnancy and the long-term health consequences of their children are thought to be linked by epigenetics, as seen here in the case of mice. Another important point to note about epigenetics is that these types of marks can be transmitted not only from a pregnant woman to her fetus but also from generation to generation if the marks are deposited in our sperm or eggs. So if you're in the audience and you're not pregnant, and you're not even thinking about conceiving, think about this, because the lifestyle decisions you make today can still affect future generations.

For example, a long-term study was conducted in Sweden and England that showed that young boys who overeated or started smoking during their pre-puberty years, when their sperm began to develop, had children and grandchildren with a significantly shorter life expectancy. . The epigenetic marks that were passed on by their diet and smoking decisions are believed to affect the long-term health of their future generations. This type of epigenetic information, of course, can also be transmitted through females to their daughters and granddaughters, if the epigenetic marks are deposited in their eggs. The idea of ​​transgenerational inheritance of epigenetic marks is still being debated and studied in terms of humans, but I must add that in non-human organisms, mice, flies, worms, there is increasing evidence that this theory is true.

In fact, it is being demonstrated in the laboratory that over dozens of generations, epigenetic marks can be transmitted from generation to generation. Another thing to know about epigenetics is that it not only affects us when we are a developing embryo, or when the sperm and egg that conceived us were developing, but it can also affect us after we are born. This is particularly relevant when we think about our brains, which continue to grow and develop throughout our lives. Let's take this example of rats. Rats contain a gene called glucocorticoid receptor and this gene can be expressed or read in a certain region of the rat's brain.

When this is the case, it helps the rat cope with stressful situations. So, the more receptor the rat has in this region of the brain, the better it will handle stress. Studies have shown that interactions between a mother rat and her pups during the first week of their life can have long-term consequences on the amount of glucocorticoid receptor that those pups will have in their brains when they grow up and, therefore, how well they will handle it. stress. Is that how it works. When rat pups are born, their glucocorticoid receptor gene is surrounded by several of these silencing epigenetic marks.

This effectively deactivates the gene. However, if a mother rat licks and grooms her offspring a lot, she basically takes good care of them, during the first week of her life, those epigenetic silencing marks can be removed from the gene. This allows the glycacoid receptor gene to turn back on and stay on in the brains of those puppies throughout their lives. Thus, when they grow, they become well-adapted animals that withstand stress well. If a mother rat ignores her offspring (Laughter), that glycocoid receptor gene will maintain those silencing epigenetic marks, they will not disappear and will remain in the brain of those offspring throughout their lives.

These rats will grow up very anxious in stressful situations. This actually raises a really encouraging point about epigenetics, since epigenetic marks are reversible. So if you've been sitting in the audience cursing your parents and grandparents for their poor lifestyle choices, or for the lack of licks and care (Laughter) you received as a baby, take heart because scientists are doing fantastic things. . Advances in the design of drugs that can reverse toxic epigenetic marks to help combat certain diseases. This seems especially promising in the case of certain cancers that are affected or activated by aberrant epigenetic marks. Here's how this can work.

Our bodies have certain genes called tumor suppressor genes. The function of these genes is to protect cells from becoming cancerous. But if too many silencing epigenetic marks begin to accumulate around these genes, the genes become deactivated and can no longer do their job of protecting the cell. So, scientists have developed drugs that have been approved by the FDA, and are in a clinical setting, that can target these silencing marks, effectively removing them from the tumor suppressor genes and allowing these genes to return to their job of protecting the tumor. cell. Now think about it. This is a radical departure from traditional cancer therapy.

Historically, we have always focused on killing cancer cells. However, this involves restoring the cells to their original nature, reminding them of what they are supposed to do. This type of therapeutic approach is also very promising in other diseases, in addition tocancer, which are also similarly affected by aberrant epigenetic marks, such as diabetes, lupus, asthma, and certain neurological disorders, such as Huntington's disease and Alzheimer's disease. I'm an optimist and think this type of therapy will hold great promise for our health in the years to come, but I must caution that one of the challenges as we move forward is figuring out how to target these drugs at the toxic epigenetic marks and leave them alone. the beneficial ones that help maintain our health.

I want to conclude by emphasizing that there are things we can do now to positively influence our epigenome. It's not too late to start eating healthier foods, foods that we already know are good for us, such as leafy vegetables, whole grains, avoiding cigarettes, cocaine and stress, all of which have been experimentally shown to negatively affect our epigenomes. These are things you can do to impact your genes and your long-term health. And if that weren't incentive enough, they can also affect the health of your future children and grandchildren. I think this concept, that we can positively impact our genes, is really profound and empowering because we have always worked under the assumption that our genes are set in stone, that they are beyond our influence.

I want to end today by challenging you, and I, to take advantage of the opportunity before us to positively impact our long-term health by treating our epigenome with kindness, through healthy lifestyle decisions. Thank you. (Applause)