Hello, everyone in this lesson. We are going to be going over X. Inactivation and dosage compensation. Okay, so let's get into it. So X inactivation is talking about actually shutting down one of the female X chromosomes. Now, why would we want to do this? We'd want to do this for the process of dosage compensation. We all know that males have this genotype, X. Y. And females have this genotype X. X. So females have twice as many X chromosomes as males. So that could become a problem if the females start making twice as many X gene products as males do, that just wouldn't work out. So the process of dosage compensation comes in and that is going to use X inactivation. So dosage compensation is a phenomenon where the gene expression of sex chromosomes is similar in both sexes. So basically whenever you're talking about dosage compensation and X inactivation, males and females will only have one active X chromosome, even though females technically have two X chromosomes. So dosage compensation makes up for the fact that different sexes have different chromosome numbers or unique chromosome numbers. They have a different number of sex chromosomes. Females have two X. S. Males have one X. So X inactivation is going to be the bulk of what we're talking about. Whenever we're talking about dosage compensation. So X inactivation basically just shuts down one of the X chromosomes forming this bar body. So what's going to happen is one of the X chromosome is not going to be utilized and it's going to be turned into a bar body now in human beings which X chromosomes is inactivated is actually random. So if you are a female, you are composed of some of your cells having your maternal X from your mother and your paternal X from your father. But about half of the cells in your body have the maternal X activated. About half of the cells in your body have your paternal X activated. But even though that is the case in most mammals, some mammals, like mice, actually only activate one X or the other mice will only activate their maternal X. And they will shut down the paternal X. But in humans it is going to be random. So I'll write that down. So in humans it is a random selection and about half are from your mother and half from your father. So the way that the X chromosome is going to be inactivated is going to be by utilizing this very important center inside of the X chromosome itself. And this is the X. Inactivation center on the X chromosomes. Now, this is going to hold very important genes that are utilized to inactivate the X. Both X chromosomes will have this center, but not both X chromosomes will utilize this center, everyone is going to utilize it and it is absolutely required for inactivation. If it is not present, a female will not inactivate her chromosomes. If it is mutated and it is placed in an unusual location in the chromosome, it may be that the wrong chromosomes are inactivated. For example. Sometimes if this center is mutated, Auda's OEM will actually be inactivated. So one of the other chromosome that does not accept chromosome. So the X. Inactivation center has to be in the perfect location for X. Inactivation to occur. Okay guys, and the way that X inactivation is going to occur is it's going to utilize his stones. It's going to utilize the methylation and it's going to utilize this very important gene called the exist gene or the X. I. S. T. Gene. So just you guys know X inactivation, let me write this down. Is going to use his stones methylation and the cyst or X. I. S. T. Gene. Okay, so his stones are DNA binding proteins and in an X. Inactivated chromosome or an inactivated X. You're going to see the his stones bind more tightly to the D. N. A. And cram it more tightly so that it's not easily transcribed. Now methylation is where they're going to be methyl groups or CH three groups added to the D. N. A. This is going to not allow transcription to happen either if DNA is methylated, it's very very difficult to transcribe and express. And then on top of that to ensure that it is entirely inactivated. The X. I. S. T. Gene is going to be utilized to cover the inactivated X chromosome in these RNA gene products and the way it happens is the X. I. S. T. Gene produces an RNA molecule that coats the X. Chromosome and in activates it Now it's sometimes hard to remember the names of these particular genes. So I just want you guys to know that X. I. S. T. Actually stands for something X. I. S. T. It's going to stand for this X. Inactive specific transcript because this is the very specific transcript that is utilized to inactivate that X chromosome. So that's what it stands for. Now. That is going to be fully expressed in the inactivated X chromosome. And what's going to happen is it's going to create this RNA molecule that will bind to the inactive X. To ensure that no other replication or no other expression machinery can actually bind to that X. Chromosome and express it. So it's fully inactivated because it has his stones very very tightly bound to it. It's methylated and it's covered in this RNA from this X. I. S. T. Gene. So there's no way that any of those genes can be expressed. And you guys can actually see that happening down in this figure right here. You guys can see that we're going to have our two X chromosomes here and then one of them is going to become the bar body. So this is the inactive X. So let me write that this is the inactive X. And it's gonna be covered with the X. I. S. T. E. R. N. A. Which is there in red and it's completely covered in the X. I. S. T. E. R. N. A. And it's going to be completely covered in his stones and methyl group. So it cannot be expressed. And then it's going to turn into this bar body. So it's going to really be shrunken down into this hetero chromosome that is not easily expressed. Now there's going to be a gene that counteracts the X. I. S. T. Gene on the active X. Chromosome. And this is going to be the T. S. I. X. Or tisk gene. And it's basically if you guys look at the names they're opposite of one another and that's because they're going to do opposite jobs. So the T. S. I. X. Gene is going to prevent X. Inactivation. So prevents X. Inactivation on the active X chromosome. Now the way that it does this is that it creates an anti sense RNA that is complementary to the X. I. S. T. E. R. N. A. Let me write that down. So the T. S. I. X. Gene makes R. N. A. That is anti sense R. N. A. To the X. I. S. T. E R N. A. Because remember the X. I. S. T. E. R. N. A is going to be utilized to completely cover the inactive X. To make sure that it turns into a bar body. But we don't want that to happen on our active X chromosome. So the T. S. I. X. Gene also makes an RNA. But it's gonna be an RNA that has come complimentary to the X. I. S. T. E R. N. A. And this ensures that the X I. S T E R N. A cannot bind with the active X chromosome because it's making this T. S. I. X. R. N. A. So the anti sense RNA and the X. I. S. T. RNA molecules are also going to help recruit proteins to the X. Chromosome which help them form the bar body which helped them compact that particular inactive X chromosome down into its very hetero chromatic, very small form. So this is going to be how mammals are going to inactivate one of their X chromosomes to ensure that the females do not have more X chromosome gene products than the males do because fema I have two X chromosomes while males simply have one. So this is the process that they are going to undergo to turn one active X into an inactive bar body to ensure that there's only one active X. Creating gene products in the female. And this is going to be the process of dosage compensation and X inactivation. Okay, everyone let's go on to our next topic.
Purpose of X Inactivation
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Okay. So this question says, why must one of the X chromosomes in the human female undergo X inactivation? Is it because all the X chromosomes are dominant or all the files on X chromosomes are dominant? Because of dosage compensation? Because X chromosomes alleles are all recessive or because the X chromosome is not needed for normal development? Well, very clearly, d can't be it. The X chromosome is of course needed for normal development. So now we have to determine is it because they're dominant recessive or due to dosage compensation? And the answer here is the dosage compensation is the reason why the X. And activation has to occur. Um The X chromosome contains can contain dominant or recessive alleles and that has nothing to do with the one that gets inactivated. So with that let's move on.
Regions of X Chromosomes
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Okay, So which of the following are which is not a region of the X chromosome required for X. Inactivation? The X. I. See, the X I. S. T, or the T. S. I X. So all three of these are regions on the X chromosome, but two of them are required for X. Inactivation, and one of them is not. So which one is not? Right? See So see this is actually required um to prevent exit activation so completely the opposite. So with that, let's move on.