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  • Hi. It's Mr. Andersen and in this video I'm going to talk about epigenetics.

  • In science there's this age old question, are you the way you are because of nature

  • or nurture? In other words, am I the way I am because of the genes I inherited from my

  • parents or from the experiences I have during my life. And a great place to study this is

  • using identical twins. And so if I had an identical twin, we would have exactly the

  • same DNA. But we wouldn't look exactly the same. And that's because during our life we're

  • going to have different experiences. Get different nutrients at different times and so we would

  • be different. And so nurture is important but so is nature. But what we're finding is

  • that the delineation between nature and nurture is blurred. And a great study that relates

  • to that and epigenetics came out in 2003 when they were looking at mice. And so this is

  • going to be a typical mouse. It's grey in color. And it's going to be relatively thin.

  • It's a normal mouse. But there's a mutation found in mice called the agouti mutation.

  • You have the agouti mutation, you're not going to be dark in color. You're going to be this

  • kind of yellowish color and you're going to be fat. You're going to be obese. And associated

  • with that, you're going to have a higher incidence of diabetes. You're going to live a less amount

  • of time. And what they found is that the scientists could actually take cloned mice, mice that

  • were exactly the same and by feeding the mother different amounts of nutrients, they could

  • produce agouti mice. In other words they could produce mice that are genetically identical.

  • So they have the same exact DNA. But they're going to express different genes. And so that's

  • what epigenetics is. It's taking the genes that we have and manipulating those. And we've

  • known about this for a long time. And so if we look at some stem cells. These are stem

  • cells here. Those are going to become the cells that are eventually an adult. They're

  • going to have all the same DNA in all the stem cells. But we know that as those cells

  • eventually start to become different cells and different cells and different cells, they're

  • going to differentiate. They're going to turn into different cells. And so the DNA is going

  • to be the same between all of those cells. But the genes that they express are going

  • to be different. And so what they have is they have all the messages to make all the

  • different types of cells inside the DNA but they're not expressing all of those. And so

  • what is epigenetics? Epigenetics is controlling which genes we're going to express at which

  • time. And so if we express just the lip genes, then we're going to make a lip cell. And if

  • we express just the eye genes, we're going to make an eye cell. And if we express the

  • ear genes were going to make an ear. But if we express all of them at the same time we're

  • going to make a cell that clearly doesn't function. And so this is something interesting

  • that you should know. That all of our cells have the same exact DNA. But they're not expressing

  • all of the genes at the same time. We call that differentiation. How do we control what

  • genes are actually being expressed? It is called epigenetics. And so we finally come

  • up with a definition for it. And if I were to read it out its "Stably heritable phenotype

  • resulting from changes in a chromosome without alterations to the DNA sequence." What does

  • that mean? Well remember phenotype is going to be the physical appearances that you have.

  • And so what epigenetics does is allow us to change the phenotypes without changing the

  • underlying DNA sequence. And this is heritable. In other words once we change that you can

  • actually pass that on to the next generation. And so before we talk about the specifics

  • of how epigenetics works, we should really talk about what DNA is. So DNA remember is

  • going to be a code and it's code to make all the proteins inside the cell. It's found in

  • all life. But DNA just doesn't sit loose within the nucleus. It's made up of something called

  • chromatin. And chromatin is basically two things. You have the DNA, which is going to

  • be the genetic code. And then you're going to have these proteins. They're called histone

  • proteins. And the DNA is wrapped around the histone proteins. The histone proteins are

  • wrapped around themselves. You eventually get threads and fibers. And you eventually

  • get what we think of as a chromosome. And so what is a chromosome? It's a bunch of proteins

  • with DNA kind of wrapped around it. And so in epigenetics what we want to be able to

  • do is to express specific genes. And so how do we do that? There's basically three mechanisms

  • of epigenetics. And the first one is called DNA methylation. So what does methylation

  • mean? It means we're adding a methyl group. We're adding a functional group. In this case

  • we're adding it to cytosine. So remember DNA is going to be made up of four different nucleotides.

  • We have adenine, cytosine, guanine and thymine. And the one I'm talking about right here is

  • called cytosine. So this is going to be a nitrogenous base. It's going to be those rungs

  • on the inside of a ladder. And if we methylate cytosine what that really means is we're adding

  • a methyl group. You can seen the methyl group right here. We're adding a methyl group to

  • the cytosine nucleotide which is going to be found on the inside of the DNA. When we

  • do this, when we methylate cytosine, it's almost like turning a switch off. So we're

  • turning that gene off. And so basically RNA polymerase now can't grab on to the DNA. It

  • can't make RNA and it can't make those proteins. And so once we methylate our DNA, we are turning

  • it off for good. Now where is it a good example of this? Well this is going to be a fertilized

  • egg or a zygote. That eventually makes stem cells. And those stem cells eventually are

  • going to differentiate to make all of the cells in our body. But how does it do that?

  • Well again it does that by methylating the genes. And so inside the circulatory system,

  • let's say a heart cell, we're going to methylate all the genes that don't make that heart cell.

  • And so the same thing is going to happen in all of the cells in our body. Now an interesting

  • thing, well how do we make those stem cells in our children again? Well when we're forming

  • those cells, those gametes cells, we're going to demethylate the DNA. So we're going to

  • remove the methyl groups and now it can become a stem cell again. So that's one mechanism.

  • Histone acetylation is going to be another one. So remember we said the DNA is wrapped

  • around these histone proteins. And so how tightly is that DNA is wrapped is going to

  • determine if we can express the genes on the DNA or not. And so if the DNA is wrapped really

  • tightly then RNA polymerase can't get on. We can't transcribe those genes. And so that's

  • controlled by a couple of different enzymes. And so before we get to the enzymes, we should

  • talk about what a histone is. A histone is going to be a protein. So it's made up of

  • a number of different amino acids, but the important ones are going to be lysine. So

  • lysine is going to be a specific amino acid. You could see here's the R group hanging off

  • the end. And what we could do is we can add an acetyl group to that. As we add an acetyl

  • group to that, right down here, what that's really going to do is it's going to change

  • the structure of these histone proteins. And that's going to loosen up the DNA that's attached

  • to it. Once we loosen up that DNA then we can start to transcribe the genes that are

  • found wrapped around the histone. It's almost like having thread wrapped around a spool.

  • And if we loosen up that thread, then we can start to code for those genes. What if we

  • don't want to express those genes? Well we're going to go in the other direction. We're

  • going to remove that acetyl group. And so the functions, or excuse me, the enzymes are

  • going to be histone, acetyl transferase. And that enzyme is going to transfer an acetyl

  • group on to the histones. And then we're going to have histone deacetylase. And so that's

  • going to remove the histone group. And so again, what does that mean? If we add the

  • acetyl group to it, then we can code for the genes here. If remove the acetyl group, then

  • RNA polymerase can't get on to the DNA and we're not going to code for it. And so this

  • is occurring all of the time. It's not like methyl groups when we're just turning a gene

  • off permanently. We're constantly acetylating and deacetylating those histones. And so we're

  • coding for the genes. And then we're not. And then one other important thing that we're

  • starting to discover is something called microRNA. MicroRNA is little bits of RNA. And so let's

  • kind of figure out where we are. This is the nucleus. So this would be a eukaryotic cell.

  • This is going to be the RNA. And then this is going to be a ribosome. Ribosome remember

  • is going to translate that protein. And so what we also produce inside our DNA is we're

  • producing a bunch of microRNA. MicroRNA is little bits of RNA that aren't going to code

  • for specific proteins. What they're going to do is they're going to bond to the regular

  • messenger RNA. When they do that they block the ribosome. And so we can't code for those

  • specific enzymes. Can't code for those specific proteins. So it's another way that we can

  • say, okay we've got the DNA. We've got the gene, but we're not going to make the protein

  • because we're going to control that post-transcriptionally after the RNA has been made. So why is this

  • important? Well it's super important that you take care of your genome. Because that's

  • what you hand on to your kids. But what we're finding is it's your epigenome thats incredibly

  • important. And so we can mess up our genome using all of these things over here. Changes

  • in diet, drugs, getting older. All those things are going to change what genes we're actually

  • expressing. And the neat thing about that and the scary thing about that is that we

  • pass that on to the next generation. And so diabetes, we found forever that diabetes is

  • going to be much more common if you have a parent who has diabetes. Well, what's going

  • on? They're actually changing their epigenome. They're changing what genes they're expressing

  • and then they're handing that off to their kids. It's a little bit scary, but that's

  • epigenetics. It's really cool. It's revolutionizing a lot of the ways we look at health problems.

  • And I hope that was helpful.

Hi. It's Mr. Andersen and in this video I'm going to talk about epigenetics.

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エピジェネティクス (Epigenetics)

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    Kelvin に公開 2021 年 01 月 14 日
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