X-Inactivation - Online Tutor, Practice Problems & Exam Prep

X inactivation is a crucial process in dosage compensation, where one of the two X chromosomes in females is randomly inactivated to ensure equal gene expression with males, who have one X chromosome. This inactivation forms a Barr body, utilizing the X inactivation center and the XIST gene, which produces RNA that coats the inactive X. Methylation and histone modifications further prevent transcription. The TSIX gene counteracts this process on the active X chromosome, ensuring proper gene regulation and maintaining balance in gene products between sexes.

X-Inactivation

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 about actually shutting down one of the female's 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, XY, and females have this genotype, XX. So females have twice as many X chromosomes as males. That could become a problem if 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. 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 2 X chromosomes. Dosage compensation makes up for the fact that different sexes have different chromosomal numbers or unique chromosomal numbers. Okay? They have a different number of sex chromosomes. Females have 2 Xs, 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 Barr body. So what's going to happen is one of the X chromosomes is not going to be utilized and it's going to be turned into a Barr body. Now in human beings, which X chromosome 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 and 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 are 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. Only one 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, an autosome will actually be inactivated. So one of the other chromosomes that is not a sex 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 histones, it's going to use methylation, and it's going to utilize this very important gene called the Zist gene, or the XIST gene. So, just so you guys know, X methylation, and the CisP or XIST gene. Okay? So, histones are DNA-binding proteins. And in an X inactivated chromosome, or an inactivated X, you're going to see the histones bind more tightly to the DNA and cram it more tightly so that it's not easily transcribed. Now, methylation is where there are methyl groups or CH3 groups added to the DNA. 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 XIST gene is going to be utilized to cover the inactivated X chromosome in these RNA gene products. And the way it happens is the XIST gene produces an RNA molecule that coats the X chromosome and inactivates it. Now, it's sometimes hard to remember the names of these particular genes, so I just want you guys to know that XIST actually stands for something. XIST is 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 histones very, very tightly bound to it. It's methylated and it's covered in this RNA from this XIST 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 2 X chromosomes here, and then one of them is going to become the Barr body. So this is the inactive X. So let me write that. This is the inactive X, and it's going to be covered with the XIST RNA, which is there in red. And it's completely covered in the XIST RNA, and it's going to be completely covered in histones and methyl groups, so it cannot be expressed, and then it's going to turn into this Barr body. So it's going to really be shrunken down into this heterochromatin that is not easily expressed. Now, there's going to be a gene that counteracts the XIST gene on the active X chromosome, and this is going to be the TSIX or TSIX 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 TSIX gene is going to prevent X inactivation. So, it prevents active X inactivation on the active X chromosome. Now, the way that it does this is that it creates an antisense RNA that is complementary to the XIST RNA. Let me write that down. So, the TSIX gene makes RNA that is antisense RNA to the XIST RNA. Because remember, the XIST RNA is going to be utilized to completely cover the inactive X to make sure that it turns into a Barr body. But we don't want that to happen on our active X chromosome. So the TSIX gene also makes an RNA, but it's going to be an RNA that is complementary to the XIST RNA and this ensures that the XIST RNA cannot bind with the active X chromosome because it's making this TSIX RNA, so the antisense RNA. And the XIST RNA molecules are also going to help recruit proteins to the X chromosome, which help them form the Barr body, which help them compact that particular inactive X chromosome down into its very heterochromatin, 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 females have 2 X chromosomes while males simply have 1. So this is the process that they are going to undergo to turn one active X into an inactive Barr body to ensure that there's only one active X creating gene products in the female, and this is going to be the process. Okay, everyone. Let's go on to our next topic.

Purpose of X Inactivation

Okay. So this question asks, 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 alleles on X chromosomes are dominant? Because of dosage compensation? Because X chromosome's alleles are all recessive? Or because the X chromosome is not needed for normal development? Well, very clearly, D cannot 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 B. Dosage compensation is the reason why the X inactivation has to occur. The X chromosome 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

Okay. So, which of the following, or which is not a region of the X chromosome required for X inactivation? The SIC, the XIST, or the TSIX. 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. C. So, C, this is actually required to prevent X inactivation, so completely the opposite. So with that, let's move on.

Here’s what students ask on this topic:

What is X inactivation and why is it important?

X inactivation is a process where one of the two X chromosomes in female mammals is randomly inactivated to form a Barr body. This is crucial for dosage compensation, ensuring that females, with their two X chromosomes, do not produce twice as many X-linked gene products as males, who have only one X chromosome. This balance in gene expression between sexes is vital for normal development and function. The inactivation involves the XIST gene, which produces RNA to coat the inactive X chromosome, along with methylation and histone modifications to prevent transcription.

How does the XIST gene contribute to X inactivation?

The XIST gene plays a central role in X inactivation by producing an RNA molecule that coats the X chromosome designated for inactivation. This RNA coating prevents the transcription machinery from accessing the DNA, effectively silencing the chromosome. Additionally, the XIST RNA helps recruit proteins that modify histones and add methyl groups to the DNA, further ensuring that the inactivated X chromosome remains tightly packed and transcriptionally silent. This process is essential for maintaining balanced gene expression between males and females.

What is the role of the TSIX gene in X inactivation?

The TSIX gene counteracts the XIST gene on the active X chromosome. It produces an antisense RNA that is complementary to the XIST RNA, preventing the XIST RNA from binding to the active X chromosome. This ensures that the active X chromosome remains transcriptionally active and does not get inactivated. The TSIX gene thus plays a crucial role in maintaining the balance of gene expression by ensuring that only one X chromosome is inactivated in females.

Why is X inactivation random in humans?

In humans, X inactivation is random to ensure that there is an equal chance of either the maternal or paternal X chromosome being inactivated in each cell. This randomness results in a mosaic pattern of X chromosome expression, where approximately half of a female's cells express genes from the maternal X and the other half from the paternal X. This random inactivation helps maintain genetic diversity and balance in gene expression, which is crucial for normal development and function.

What mechanisms are involved in the inactivation of the X chromosome?

The inactivation of the X chromosome involves several mechanisms: the XIST gene produces RNA that coats the X chromosome, preventing transcription; histone modifications, where histones bind more tightly to the DNA, making it less accessible; and DNA methylation, where methyl groups are added to the DNA, further preventing transcription. These mechanisms work together to ensure that the inactivated X chromosome remains transcriptionally silent and forms a compact structure known as a Barr body.