Epigenetic Regulation of Gene Expression

Hi in this video we're gonna be talking about the epigenetic regulation of gene expression. So we've talked about ePI genetics before and I just want to reintroduce these concepts and a few of these terms so that we can add some more information about it in relation to how it controls gene expression. So first we remember what epigenetic regulation is or just epi genetics in general. Right? Epigenetic refers to the modifications that occur on his stone proteins and that can affect the D. N. A. Structure and in this case control gene expression. So there are a couple of different modifications of histone proteins that can occur. And we've talked about these before but like I said I just want to add a little bit more information um about specifically gene expression. So the two types of modifications that we've talked about before are histone methylation and histone acetyl ation. So um remember histone methylation is the addition of a methyl group onto certain amino acids on histone protein. And so there are the information that I want to add about histone methylation is this concept of CPG islands. So what our CPG islands. These are C. And G. Nucleotides um that are either repeats or just sort of high percentages of CNG nucleotides somewhere in the genome that remain unmet related. So why am I telling you about a new methylated C. G. T nucleotides because we're supposed to be talking about methylation while I'm telling you about the unventilated ones because most cG sites recruits these proteins called methyl transfer aces which bring in and cause histone methylation. So the majority of the C. G. S in the genome have some type of methylation on them. But C. G. CPG islands are different because they remain unmet dilated. And so the reason that they remain unventilated is because they're in promoter regions and these promoter regions have this high gc content. But because the promoters they promote gene expression so they really can't be methylated or the gene would be expressed and so normally um so histone methylation is responsible for repressing um repressing gene expression by stimulating chromosome condensation. Um If you remember the chroma team gets really tight when it's methylated. Um And so we don't want that methylation at promoter regions. And so CPG islands have evolved that R. C. G. Nucleotides that remain in methylated. Now histone acetyl ation is the addition of a Seattle group certain amino acid on histone proteins. Remember this stimulates some kind of open chrome aton structure so not tight but open so that transcription can occur. So trans like genes that are very actively transcribed have a lot of assimilation on them. And so um the process of histone insulation happens through proteins called histone acetyl transfer aces. Um And then assimilation can be removed by histone D. Acetyl aces which you may see abbreviated as H. D. A. C. So added is a Seattle transfer ace and then removal is dsc Dsc delays Now the histone code which is this folded word here refers to the combination of methylation and assimilation that regulate chroma captain structure and then therefore gene expression. And so the histone code sort of controls you know what regulatory proteins actually get to the gene are those ones that are stimulating gene expression or repressing it. And his own code is really complex because there's so many different modifications that can be made. So um since the CPG islands is kind of a new concept and we haven't talked about it. I wanted to show an image about it. So here we have each one of these lines here is a sort of a C. G. Site in the genome has lots high amounts of C. And G. But and then these yellow things here are ones that become methylated. So these are methylated, the key is here but in case you don't want to pay attention to it and I'll just tell you um so these are methylated. So over time you can see that the methylated um CMg eventually sort of disappear or just you know, become other nucleotides because they're methylated, they're not being transcribed. So they're not having this um you know constant need to stay the exact same. So they get mutated and change and essentially some of them remain. But generally only the CPG islands that remain unmet dilated because they're in promoter regions are the ones that have really the IAN methylated cG regions that have remained in the genome today. So that's kind of how CPG islands evolved and what they are. And they're very commonly found in these promoter regions because they need a new methylated C. And G. S. In order to promote the transcription of the gene. Sorry just drove like you now um with epigenetic regulation comes different proteins that can act as genetic activators or repressors. So histone modifications can sort of condense an open chrome aton. But the the open chrome aton or the condensed chromosome really isn't gonna do anything unless it brings in proteins that can stimulate transcription. And so most of these activator and repressor proteins actually can modify the chromosome structure itself to support the gene expression. So so here we're mostly talking about kind of moving either histone modifications around to different histone, we're actually moving the nuclear zone itself. So one of the things that does this is called the nuclear zone or chroma tin remodeling factors. You may see it, crow metin remodeling factors or nuclear zone. Um And they do exactly what they sound like they do. They rearrange nuclear zones and so they don't actually affect methylation or assimilation. The nuclear ISMs remain the same. You know have the same histone code that they had before but they're just moved to a different DNA location. So they're either moved down or moved up or just slightly elongated so that you know D. N. A. Is differently attached to the nuclear zone. Now there are other factors called elongation factors and these are factors that modify his stones by sort of disrupting nuclear zones during transcription. And so transcription of the genes are already being transcribed. But if you modify you know how tightly the nuclear zone is controlled then that's going to potentially prematurely stop transcription and prevent that gene from being expressed. So elongation factors or things that you know affect transcription as it's happening by affecting the nuclear zone. And so these proteins, both the nuclear zone chromosome remodeling factors or the elongation factors typically reside actually on the RNA polymerase tail. So these are things that are acting during transcription to mess up the nuclear zone in some way to either allow or restrict access to the D. N. A. So um there's another term here that I want to talk about. Um and that synergy and what that means in terms of gene expression. So a lot of times activator proteins work synergistically. So what this means is or transcription synergy is when several activator proteins come together to increase the rate of transcription. And um transcription synergy is usually only described when the new rate to the rate of all the proteins working together is higher than if we just added the rate of every protein individually. So if we have say four proteins here and each of them increase transcription by two times. This would normally just say we're just adding these. This would be eight so eight times higher if we're just adding them together. But transcription synergy would be if the actual rate of all four working together was 12 times higher. So it's more than adding them together but it's still increasing the rate of transcription. So let's look at this image here back up. So what you can see is there's we have closed chroma tonight. So this is going to be chrome button, that's what methylated or see related right? It's going to be methylated and we have relaxed chroma tin and that's gonna be the opposite remember this is gonna be assimilated and you can see them here And so we have to remember the H G A C removing the assimilation here. Um We have a situation coming on to cause the different states but essentially both of these um pathways result in altered gene transcription and so you don't need to know anything about this down here. This is just kind of extra. But just know that these two different states alter gene um transcription and gene expression. So now let's move on.

Hello everyone. In our last lesson we talked about different epigenetic mechanisms that alter gene expression in this lesson, we are going to be learning how those epigenetic mechanisms can be passed down from cell to cell or organism to organism. So we're going to be talking about epigenetic heredity because there are ways that these chromosome structure can be inherited from cell to cell or parent to offspring. Generally, when we think about heredity, we think about passing down genes, genetic code, genetic information. We don't generally think about passing down the chroma tin structure or the way our DNA is wrapped around certain proteins. We don't really think that that's a form of heredity but in fact it is and it's called epigenetic heredity. And one example of epigenetic heredity is going to be how cells differentiate. So remember that sells terminally differentiate, meaning that after differentiation the daughter cells created can only be one cell type. So for example, if you have a cell that is a liver cell that has differentiated terminally it will only ever be a liver cell and all of the daughter cells that it creates are going to be liver cells. So it has terminally differentiated. It can only make liver cells. This is terminal differentiation. So this is called cell memory because there are certain genes that are only expressed in liver cells. There's certain genes that are expressed in liver cells and certain genes that are silenced. And this is to do with the liver cells function only the genes that are needed for liver function are going to be created or expressed in these liver cells. So the daughter cells have to remember the expression pattern of those particular genes. So cell memory is the property that allow cells to pass patterns of gene expression to their daughter cells. This is how liver cells only make other liver cells or skin cells only make other skin cells because they're passing down these patterns of gene expression. So those cells only express the genes needed for that particular tissue. This is a form of epigenetic heredity because this is going to include methylation a set elation, how tightly the chroma tin is wound in certain areas. How lucid is in certain areas because this is going to alter which genes are transcribed and which ones are not. So this heredity does not include D. N. A. Sequence. But instead the crow metin modifications that we talked about in our last lesson Now another example of epigenetic heredity is going to be epigenetic inheritance and this is not from cell to cell. This is from parent to offspring. So epigenetic inheritance is the property that allows organisms to pass patterns of gene expression onto their offspring. Again, this does not include the D. N. A. Sequence. This is only talking about the crow metin modifications where those settle ations, those methylation silencers activators where all those proteins and those modifications are and how the chroma teen is structured. So a great example of epigenetic inheritance is genomic imprinting certain genes in the human body. Not too terribly many but certain genes in the human body are imprinted and imprinting is pretty common in all types of organisms imprinted means that one of the alleles you get from your parents is inactive and one of them is active. So the reason one allele is active and one allele is not active is due to epigenetic mechanisms is due to chromatic modifications. So genomic imprinting is when one parental copy remains active while the other remains inactive. Now genomic imprinting can be that for a particular gene it is always the mother's gene that is active or it's always the father's gene that is active. This is genomic imprinting inactive copies remain methylated depending on the source and two identical DNA sequences can have different chromatic modification structures. These are the same two genes, just one is from your mother and one is from your father and depending on which person they're from is going to give you a certain chromosome modification for that khalil, your parents are passing on their chrome it's and modifications to you. And if one of the genes is imprinted and silo and one of them is not then they are passing those chromatic modifications on to their offspring. So this is epigenetic inheritance. This doesn't change the sequence of the gene. They're the exact same genes just one is expressed and one is not depending on methylation or non methylation. So an example of this you can see in these little mice here is the altered methylation status of this particular gene and this is going to cause drastically different phenotype in genetically identical mice. These mice are actually, I believe they're identical twins, but the scientists changed the gene expression in this mouse and you can see that this twin completely different color. It's like blonde while the other one is brown and it's much larger. So they actually changed the methylation states of particular genes in this organism. And it came out with a completely different phenotype than its identical twin. So this is going to be a great example of ePA genetics in the in science in labs, we can actually change chromosome structure and change the phenotype of certain organisms. Okay, so now we're going to go to another example of epigenetic mechanisms which is going to be chromosome wide chroma tin structure changes. So this means that the whole chromosome has a particular chroma tin structure. The greatest example of this is going to be X. Inactivation X. Inactivation is going to happen in females, females have two X chromosomes and male have an X. And a Y chromosome. And if you remember anything about those particular chromosomes, the X chromosome is substantially larger than the Y chromosome. So because the female has two X chromosomes and the male only has one, she has a lot more genetic material than he does in those particular in those particular chromosomes. So in the female, one of the X chromosomes is going to become inactivated. This is X inactivation. This is the transcription inactivation of an entire chromosome. One of the two X chromosomes that a female has now, which X is inactivated is random. So there's no rhyme or reason, it's just a random mixture meaning that both X copies have the same chance of being inactivated. So whenever the embryo, a female embryo is developing, once there's a couple 1000 cells then the embryo will begin shutting off some of its excess and it will be a random array of which excess will be shut off. But once a cell chooses which X it is shutting off which exit is in activating. It remains inactive for the rest of cellular division. So once those cells in the female embryo determine which X will be inactivated, every daughter cell made from those cells are going to have the same X inactivated. I hope that makes sense. I know that's kind of confusing. But you're going to have the same pattern of inactivation throughout the cell divisions throughout the daughter cells. So this is inherited epigenetic modification of an entire chromosome through the cellular lineage. And remember like I said, X activation occurs after a few several 1000 cells have formed. Then they're going to randomly shut off one of their exes And then every cell made from those few 1000 cells is going to remember which ex was inactivated in the parent cell. I hope. That's not too confusing. It is a really cool mechanism though. And this mechanism is responsible for some really cool phenotype, especially if there are phenotype of skin color for color, eye color that correlate with the X. Chromosome. And these can create mosaic phenotype where each cell chooses a different X chromosome that it in activates. And the alleles on each copy encode for a different appear. And a great example of X. Inactivation, creating a mosaic phenotype is going to be in this calico cat. If you've ever seen a calico cat or if you know anything about calico cats, they have these splotchy different color patterns. They're black, orange, gray, white, they'll have the splotches all over them. But I don't know if you all know this calico cats are only female because only females can have this mosaic pattern because only females have X inactivation and one of the fur color jeans is on her X chromosomes. So she has the splotchy pattern because there are different X chromosomes being inactivated in the different colors of her firm based on when she was an embryo and then which sells decided to inactivate, which which sounds kind of crazy but it is pretty cool. So this is a calico cat. If you wanted to look up anything about them, they are pretty cool. But this is one example of X inactivation in a very visible phenotype which is really neat to see. So that's going to be some great examples of epigenetic inheritance. And remember that this is not changes injun genetic code. This is going to be the inheritance of chroma tin structure, how condensed how loose certain areas of chroma genes are, and this is going to alter which genes are expressed in which genes are silenced, either in certain daughter cells or in entire organisms. Okay, everyone, let's go on to our next topic.