Epigenetic Regulation of Gene Expression - Online Tutor, Practice Problems & Exam Prep

Epigenetic regulation involves modifications like histone methylation and acetylation that influence gene expression by altering chromatin structure. Unmethylated CpG islands in promoter regions promote transcription, while methylation typically represses it. Epigenetic heredity allows these modifications to be inherited, affecting cell differentiation and genomic imprinting, where one allele is silenced based on parental origin. X inactivation in females exemplifies this, leading to mosaic phenotypes, such as in calico cats, showcasing how chromatin structure impacts gene expression without altering the DNA sequence.

Epigenetic Modifications

Hi. In this video, we're going to be talking about the epigenetic regulation of gene expression. So we've talked about epigenetics 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, do we remember what epigenetic regulation is or just epigenetics in general? Right. Epigenetics refers to the modifications that occur on histone proteins, and that can affect the DNA 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, about specifically gene expression.

So the two types of modifications that we've talked about before are histone methylation and histone acetylation. So, remember histone methylation is the addition of a methyl group onto certain amino acids on the histone protein. And so there are the information that I want to add about histone methylation is this concept of CPG islands. So what are CPG islands? These are C and G nucleotides that are either repeats or just sort of high percentages of C and G nucleotides somewhere in the genome that remain unmethylated. So why am I telling you about unmethylated CG nucleotides? Because we're supposed to be talking about methylation. Well, I'm telling you about the unmethylated ones because most CG sites recruit these proteins called methyltransferases, which bring in and cause histone methylation. So the majority of the CGs in the genome have some type of methylation on them. But CG CPG islands are different because they remain unmethylated. And so, the reason that they remain unmethylated is because they're in promoter regions. And these promoter regions have this high GC content, but because they're promoters, they promote gene expression. So they really can't be methylated, or the gene would be expressed. And so, normally, histone methylation is responsible for repressing gene expression, by stimulating chromatin condensation. If you remember the chromatin gets really tight when it's methylated. And so, we don't want that methylation at promoter regions. And so, CPG islands have evolved that are CG nucleotides that remain unmethylated. Now, histone acetylation is the addition of an acetyl group to an amino acid on histone proteins. So, remember this stimulates some kind of open chromatin structure. So not tight, but open so that transcription can occur. So genes that are very actively transcribed have a lot of acetylation on them. And so, the process of histone acetylation happens through proteins called histone acetyltransferases. And then acetylation can be removed by histone deacetylases, which you may see abbreviated as HDAC. So, added is acetyltransferase, and then removal is deacetylase.

Now, the histone code, which is this bolded word here, refers to the combination of methylation and acetylation that regulate chromatin 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 the histone code is really complex because there are so many different modifications that can be made. Since the CpG islands are 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 CG site in the genome. It has 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, I will just tell you. So, these are methylated. So, over time, you can see that the methylated, C and G 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, you know, constant need to stay the exact same, so they get mutated and changed, and essentially some of them remain. But generally, only the CPG islands that remain unmethylated because they're in promoter regions are the ones that have really the unmethylated CG regions that have remained in the genome today. So, that's kind of how CpG islands evolved and what they are and they are very commonly found in these promoter regions because they need unmethylated CNGs in order to promote the transcription of the gene.

Whoops. Sorry. Let me just drive light you. Now, with epigenetic regulation comes different proteins that can act as genetic activators or repressors. So histone modifications can sort of condense and open chromatin, but the open chromatin or condensed chromatin really isn't going to do anything unless it brings in proteins that can stimulate transcription. So here we're mostly talking about kind of moving either histone modifications around to different histones or actually moving the nucleosome itself. So one of the things that does this is called the nucleosome or chromatin remodeling factors. You may see it chromatin remodeling factors or nucleosome. And they do exactly what they sound like they do. They rearrange nucleosomes. And so they don't actually affect methylation or acetylation. The nucleosomes 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, you know, elongated so that, you know, DNA is differently attached to the nucleosome. Now there are other factors called elongation factors, and these are factors that modify histones, by sort of disrupting nucleosomes during transcription. And so, transcription, the genes are already being transcribed, but if you modify, you know, how tightly the nucleosome is controlled, then that's going to potentially prematurely stop transcription and prevent that gene from being expressed. So elongation factors are things that affect transcription as it's happening by affecting the nucleosome. And so, these proteins, both the nucleosome, chromatin 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 nucleosome in some way to either allow or restrict access to the DNA. So, there's another term here that I want to talk about, and that is 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 transcriptional synergy is when several activator proteins come together to increase the rate of transcription. And, transcriptional synergy is usually only described when the new rate, so 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, this would normally just say we're just adding these, this would be 8, so 8 times higher if we were just adding them together. But, transcriptional 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 a little bit more we have closed chromatin. So these so this is going to be chromatin that's what? Methylated or acetylated? Right. It's going to be methylated. And, we have, relaxed chromatin, and that's going to be the opposite. Remember, this is going to be acetylated. And, you can see them here. And so, we have, remember the HDAC, removing the acetylation here. We have acetylation coming on to cause the different states. But essentially, both of these 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 transcription and gene expression. So now let's move on.

Epigenetic Heredity

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 modifications of chromatin 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 chromatin 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 cells 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 are 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 allows 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, acetylation, how tightly the chromatin is wound in certain areas, how loose it 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 DNA sequence, but instead the chromatin 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 DNA sequence. This is only talking about the chromatin modifications, where those acetylations, those methylations, silencers, activators, where all those proteins and those modifications are, and how the chromatin 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 chromatin 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 chromatin 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 chromatin modification for that allele. Your parents are passing on their chromatin modifications to you. And if one of the genes is imprinted and silenced and one of them is not, then they are passing those chromatin 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.

Now we're going to go to another example of epigenetic mechanisms, which is going to be chromosome-wide chromatin structure changes. So this means that the whole chromosome has a particular chromatin structure. The greatest example of this is X inactivation. X inactivation is going to happen in females. Females have two X chromosomes and males 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 chromosomes. So in the female, one of the X chromosomes is going to become inactivated. This is X inactivation. This is the transcriptional 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 are a couple of thousand cells, then the embryo will begin shutting off some of its X's and it'll be a random array of which X's will be shut off. But once a cell chooses which X it is shutting off, which X it is inactivating, 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 is going to have the same X inactivated. This is inherited epigenetic modification of an entire chromosome through the cellular lineage. And remember, like I said, X inactivation occurs after a few thousand cells have formed. Then they're going to randomly shut off one of their X's and then every cell made from those few thousand cells is going to remember which X was inactivated in the parent cell.

Okay, everyone. Let's go on to our next topic.

Which of the following is not a form of epigenetic heredity?

• A. Cell memory
• B. X inactivation
• C. CpG islands
• D. Genomic imprinting

Which of the following modifications is found most often with open chromatin?

• A. Acetylation
• B. Methylation
• C. Phosphorylation
• D. Ubiquitination

Chromatin remodeling factors move nucleosomes by altering the methylation or acetylation pattern.

• A. True
• B. False

CpG islands are groupings of CG nucleotides that are unusual because why?

• A. They are highly methylated
• B. They are unmethylated
• C. The are found in genes
• D. They are highly acetylated

Here’s what students ask on this topic:

What is epigenetic regulation of gene expression?

Epigenetic regulation of gene expression involves modifications to histone proteins and DNA that alter chromatin structure, thereby influencing gene activity without changing the DNA sequence. Key modifications include histone methylation, which typically represses gene expression by condensing chromatin, and histone acetylation, which promotes gene expression by loosening chromatin. Unmethylated CpG islands in promoter regions are crucial for transcription initiation. These epigenetic changes can be inherited, affecting cell differentiation and genomic imprinting, where one allele is silenced based on parental origin. This regulation is essential for processes like X inactivation in females, leading to mosaic phenotypes such as calico cats.

How do histone modifications affect gene expression?

Histone modifications, such as methylation and acetylation, play a crucial role in regulating gene expression by altering chromatin structure. Histone methylation typically represses gene expression by condensing chromatin, making it less accessible to transcription machinery. In contrast, histone acetylation promotes gene expression by loosening chromatin, allowing transcription factors to access DNA. These modifications are mediated by enzymes like histone methyltransferases and histone acetyltransferases, and can be reversed by histone demethylases and histone deacetylases (HDACs). The combination of these modifications, known as the histone code, determines the overall chromatin state and gene activity.

What are CpG islands and their role in gene expression?

CpG islands are regions of DNA with a high frequency of cytosine and guanine nucleotides linked by a phosphate bond (CpG sites). These regions are often found in promoter areas of genes and remain unmethylated to promote gene expression. Unmethylated CpG islands allow transcription factors to bind to the promoter region, facilitating the initiation of transcription. In contrast, methylation of CpG sites generally leads to chromatin condensation and gene repression. Thus, CpG islands play a critical role in regulating gene expression by maintaining an open chromatin structure in promoter regions.

What is epigenetic heredity and how does it affect cell differentiation?

Epigenetic heredity refers to the transmission of chromatin modifications, such as methylation and acetylation, from parent cells to daughter cells without altering the DNA sequence. This process is crucial for cell differentiation, where specific gene expression patterns are maintained in specialized cells. For example, a liver cell will pass on its chromatin structure to its daughter cells, ensuring they also function as liver cells. This 'cell memory' allows differentiated cells to retain their identity and function across generations, contributing to the development and maintenance of tissues and organs.

What is genomic imprinting and how does it relate to epigenetic inheritance?

Genomic imprinting is an epigenetic phenomenon where only one allele of a gene is expressed while the other is silenced, depending on its parental origin. This selective expression is due to chromatin modifications like methylation. For instance, if the maternal allele is imprinted (silenced), only the paternal allele will be active. This imprinting is inherited from parent to offspring, making it a form of epigenetic inheritance. It does not alter the DNA sequence but involves the transmission of specific chromatin states, affecting gene expression and potentially leading to different phenotypes in offspring.