字幕表 動画を再生する 英語字幕をプリント 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.