The Epigenetic Code: Study with Video Lessons, Practice Problems & Examples

Chromatin, composed of DNA and histone proteins, exists in two forms: euchromatin (less condensed, accessible for gene expression) and heterochromatin (more condensed, generally silent). Histone modifications, such as acetylation and methylation, influence chromatin structure and gene accessibility. The dynamic nature of these modifications allows for epigenetic changes that can be inherited, affecting gene expression across generations. Understanding this epigenetic code is crucial for grasping how gene regulation and cellular memory function in biological systems.

Chromatin Structure

Hi, in this video, we're going to be talking about the epigenetic code. So first, before we can talk about the epigenetic code, we need to know what we're talking about, and how we need to do that is to make sure we understand the definition of protein. So, what is chromatin, do you remember? Right, so chromatin is the combination of DNA plus protein. So, we're not just focused on the DNA itself. We focus on this sort of globular picture of DNA and protein, or globally globular picture of DNA and protein. And so, the chromatin, which is DNA and protein, can exist in two forms. These are euchromatin or heterochromatin. So, these two states are defined based on how condensed the DNA is, so euchromatin is less condensed, a looser DNA structure. And so, because it's not tightly packed, that allows the DNA to be accessible to other proteins. Heterochromatin, on the other hand, is more condensed. And so, that means that the genes that are found on heterochromatin are generally not expressed because it's so tightly condensed that things like transcription factors and other elements that would express genes can't bind there; they can't access the DNA. And so, these genes are not expressed; therefore, heterochromatin usually contains only a few genes. And so, heterochromatin is found mainly in regions of the chromosome that don't contain a lot of genes, including centromeres and telomeres. Now, because heterochromatin has such a strong effect of not allowing gene expression, there is this nearby region called the zone of inactivation, and this is based on how close the genes are to heterochromatin. So, the closer they are to heterochromatin, the less likely they are going to be expressed, or the less highly they are going to be expressed. So, the fancy term for this is position effects, but it just means that, you know, the closer the gene is to heterochromatin, the less it's going to be expressed. So, if we just take a second to look at this example here, you can see that euchromatin is here, and this sort of is the active form because it's not as condensed, and different proteins or things can come in, and they can bind and transcribe the gene or do whatever they need to. Whereas in heterochromatin, these genes are generally silent because they're so tightly packed that really nothing can come in here and access. There's just no points where it can bind. So, it remains silent, and the genes remain unexpressed. So now, let's move on.

Histone Modifications

So we now know about the different states of chromatin. But we haven't yet explained how they actually form those different states. And so this video is going to really focus on different protein modifications that form the different condensation states of DNA. Chromatin is made up of DNA and protein, and the majority of that protein are histone proteins. Histone proteins are responsible for packaging and condensing the DNA. This happens because each histone protein contains an interminable tail, and on this tail, there is a long string of amino acids that can be modified. These modifications affect the condensation of DNA; some modifications make it more condensed and some make it less condensed.

The two most common modifications are acetylation and methylation, and I just added in parentheses here what is actually being added — the chemical structure that's being added. Although you usually don't need to know these exact chemical formulas, just know the names of acetylation and methylation. Acetylation removes a positive charge from the histone, resulting in a loosening of the chromosome structure. The chromatin expands a little, and genes can be accessed. Methylation, on the other hand, tightens chromosome structure and can actually prevent acetylation.

If we were to do a quick practice question here, acetylation would be what's causing either loosening or tightening of protein? Right, acetylation would be loosening and methylation would be tightening.

Sometimes, when this happens, we think that each amino acid can have an acetylation or a methylation independently, but sometimes there can actually be a chain reaction. What happens there is that one amino acid gets some type of modification, either a methylation or acetylation, but because of that modification, it triggers all the rest of the amino acids down the line to have the same modification. So you get this long linear chain of similar histone modifications, which can affect a very long stretch of protein.

Although these chain reactions can't go on forever or everything would be expressed all the time, and that would just be complete destruction. Eventually, they are stopped by barrier sequences, which can separate saying, "This is condensed protein and this is non-condensed protein." Even though there's a chain reaction going on, you're stopping here because you're not going to move on to this condensed chromosome section.

Let's look at the nucleosome core. These are the histone proteins, and they are actually right now formed into a nucleosome. They all have these little tails, you can see them hanging off here with amino acids on them, and each one of these amino acids can be modified in various ways. Now, I talked about methylation and acetylation, but there are all these other types of modifications that I didn't really talk about but still exist. You can see that all of these amino acids can be modified in so many different ways and these modifications affect protein structure. So now let's move on.

Epigenetic Code

In this video, we're going to be talking about reading the epigenetic code. So we've talked about how histone proteins can have all these different modifications on them. But you can imagine because there's so many modifications and so many amino acids that reading the genetic epigenetic code, which is the histone modification code, can be extremely difficult. You know what combinations of modifications do and so each nucleosome has a different set or pattern of modification. And these modifications are actually really carefully controlled because once the nucleosome has been modified, these modifications of acetylation or methylation not only affect chromosome condensation but it can also attract other proteins which can do various things to the DNA. And so, as the cell is going, you know this is sort of a dynamic process. It's not just stationary. So as the cell needs more gene expression or less gene expression or it needs to divide all of these modifications have to constantly change to adapt to the cell's needs in order to allow replication of this DNA or expression of this gene or inhibition of this other gene. So all of these modifications are not only really complex because there are so many different of them but also very complex because they're always changing.

There is one complex called the chromatin remodeling complex and this is a complex that uses ATP energy or energy from ATP to change the position of DNA in the nucleosome. So far, we've actually just talked about amino acids and modifications but actually there's a second kind of layer of understanding the epigenetic code because the nucleosomes aren't stationary on a specific sequence of DNA. They can move to allow access or to constrict a region of DNA. And how they do this is through chromatin remodeling complexes which allow for specific DNA sequences to become more or less accessible.

Here's an example of histone remodeling. You can see here you have your nucleosomes. Yeah, here and there's this protein that wants to come in and bind. But it can't because there's a nucleosome in the way. So the chromatin remodeling complexes come in and move the histone down. So it exposes this DNA which then can move forward and do whatever it needs to do express the gene, replicate the gene, whatever. So that's how that happens.

With epigenetics there's actually this really unique thing that you've probably never heard of before which is epigenetic inheritance. And so, we can think of inheritance usually as people inheriting DNA or inheriting genes from their parents. But there's actually this whole field that really just sort of newly discovered. That's very exciting. That is actually epigenetic inheritance. So this is the fact that you can actually inherit chromatin structure. So not just the DNA and the genes itself but you can actually inherit the condensation state of the DNA. And so histone modifications can be passed on to daughter cells. So this can happen through just sort of normal cell division. So when skin cells divide, they can keep their histone modifications. But there's also some evidence that this can actually happen in germ cells when passing down to offspring. And so how this happens is like it happened with the histone codes; amino acids on the tail of the histones are covalently modified. They affect the condensation and that is passed down to either another generation of skin cells or liver cells but potentially also to offspring. So this inheritance actually allows for this process called cell memory, which is a type of non-genetic inheritance. And so we think of inheritance as being all genetic just genes being passed. But epigenetic inheritance is actually non-genetic. And the fact that just these modifications being passed down to cellular offspring. So now let's move on.

Which of the following terms is associated with condensed chromatin?

• A. Acetylation
• B. Euchromatin
• C. Heterochromatin
• D. Cell memory

Which of the following histone tail modifications is most likely to cause closed chromatin?

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

The position of nucleosomes on a region of DNA can never change.

• A. True
• B. False

Histone protein modifications can be inherited.

• A. True
• B. False

Here’s what students ask on this topic:

What is the epigenetic code and how does it affect gene expression?

The epigenetic code refers to the set of chemical modifications to histone proteins and DNA that regulate gene expression without altering the DNA sequence itself. These modifications include acetylation, methylation, phosphorylation, and ubiquitination, among others. Acetylation typically loosens chromatin structure, making genes more accessible for transcription, while methylation usually tightens chromatin, reducing gene expression. These modifications are dynamic and can change in response to environmental factors, allowing cells to adapt their gene expression profiles. Understanding the epigenetic code is crucial for grasping how genes are regulated and how cellular memory is maintained across cell divisions.

What is the difference between euchromatin and heterochromatin?

Euchromatin and heterochromatin are two forms of chromatin that differ in their degree of condensation and gene activity. Euchromatin is less condensed, making it accessible to transcription factors and other proteins involved in gene expression. This form of chromatin is generally associated with active genes. In contrast, heterochromatin is more condensed, making it less accessible and generally associated with gene silencing. Heterochromatin is often found in regions of the chromosome that contain few genes, such as centromeres and telomeres. The dynamic nature of these chromatin states allows for the regulation of gene expression in response to cellular needs.

How do histone modifications influence chromatin structure?

Histone modifications, such as acetylation and methylation, play a crucial role in influencing chromatin structure. Acetylation of histone tails typically removes positive charges, reducing the interaction between histones and DNA, leading to a more relaxed chromatin structure (euchromatin) that is accessible for transcription. Methylation, on the other hand, can either activate or repress gene expression depending on the specific amino acids that are methylated. Generally, methylation tightens chromatin structure (heterochromatin), making it less accessible for transcription. These modifications are reversible and can be dynamically regulated to control gene expression in response to various signals.

What is epigenetic inheritance and how does it differ from genetic inheritance?

Epigenetic inheritance refers to the transmission of chromatin structure and histone modifications from parent to daughter cells, affecting gene expression without altering the underlying DNA sequence. This can occur during normal cell division and potentially in germ cells, passing these modifications to offspring. In contrast, genetic inheritance involves the transmission of DNA sequences from parents to offspring. Epigenetic inheritance allows for cellular memory, enabling cells to maintain specific gene expression patterns across generations. This non-genetic form of inheritance is crucial for processes like development, differentiation, and adaptation to environmental changes.

What role do chromatin remodeling complexes play in gene regulation?

Chromatin remodeling complexes are essential for gene regulation as they reposition nucleosomes on DNA, making specific regions more or less accessible for transcription. These complexes use energy from ATP to slide, eject, or restructure nucleosomes, thereby exposing or hiding DNA sequences. This dynamic repositioning allows transcription factors and other regulatory proteins to access or be blocked from binding to DNA, facilitating or inhibiting gene expression. Chromatin remodeling is crucial for processes like DNA replication, repair, and transcription, enabling cells to respond to developmental cues and environmental changes effectively.