Epigenetics, Chromatin Modifications, and Regulation - Video Tutorials & Practice Problems

Chromatin

Hi in this video we're gonna be talking about epigenetic scrotum modifications and regulation. So um most of you are aware that D. N. A. Has to be packaged right normally our D. N. A. Is so long and just like spread out. But we see it in form of chromosomes and so it has to be packaged so that it fits into those chromosome forms and fits into the nucleus. And so some of you may have already seen the videos in which I talk about chromosome packaging um which are super important if your book presents them. But if not don't worry about it because we're gonna talk about some of the overviews here. So eukaryotic DNA packaging can regulate gene expression. So this packaging isn't just so that the D. N. A fits into the cell and can divide in the form of chromosomes but actually so that it can regulate gene expression as well. So there are two forms of chroma tin which chroma tin is defined by DNA and protein two forms. And the first is you chrome button and the second is hetero chrome button. And this refers to how tightly packaged the D. N. A. Is. So you Cro Magnon is loosely packaged and hetero cro magnon is tightly packaged. Now obviously if you have loose package D. N. A. And tightly packed DNA that's going to affect gene expression. So the law loose um D. N. A. Has all this more open space proteins can come in initiate transcription. RNA polymerase can come in and transcribed genes. So these are so you carry so you crow metin regions and the chromosome are generally where genes are being expressed, whereas hetero chroma tin is tightly packaged. And so that means that that means that all these proteins that are needed for transcription initiation for anything essentially are not going to be able to get in and so they're not going to be transcribed. These genes are not going to be expressed. So here we have an example of this you can see eukaryotic proteins can come in, they can buying to these regions and start transcribing and make these genes active. Whereas hetero comitan the proteins cannot bind to the DNA because it's so tightly packaged. So these are going to be silent and whatever's in this region, whatever is in this region of the D. N. A. Is not going to be expressed. So you might say, okay, is everything always you chroma 10 or hetero competent or does it change back and forth? And it actually changed back and forth. And so there are three types of chromatic modifications that can sort of change whether it's you chroma tin or hetero chroma tin and affect gene expression. So the first one is called chroma teen remodeling. And this is the process of removing nuclear zones to new DNA sequences. So most of you should know what a nuclear zone is but in case you don't nuclear zones are these yellow proteins here. So you can see D. N. A. Is in red and these yellow proteins are in here. So the yellow protein is called a nuclear zone and this is what D. N. A wraps itself around to package either loosely or tightly. So nuclear zones are associated with every single D. N. A sequence. It's just whether these are all packaged loosely or tightly. So cro magnon remodeling can actually move nuclear zones to new D. N. A sequences. And why would it need to do that? Well let's say that this region here has a promoter and so that promoter needs to have proteins bind to it so that it can promote transcription. Right? That's what a promoter does. But if it's wrapped around a nuclear zone this means that different factors like this blue protein here can't come in and bind it. So chrome aton remodeling will actually push this nuclear zone either this way or this way to a new sequence so that the D. N. A. Region with the promoter on it that says promoter in case you can't read my ridiculously messy handwriting. Um So that these proteins can come on buying and activate transcription. So that is chromatic remodeling. Now there's a bunch of different proteins of course that are responsible for moving those nuclear zones either this way or this way. Um But the main really important one you should know about is the S. W. I. S. And F. Complex. The protein complex meaning it has a lot of different proteins in it and they reposition nuclear ISMs so that is the first type of chromosome modification. Let's turn the page and get to the second.

Histone Protein Modifications

Okay, so now we're gonna talk about histone protein modification. So just in case you need a refresher water histone proteins, do you remember where they are? Right, they are in the new clio zone and that is what the D. N. A. Is wrapped around to be able to package. So histone protein modifications can affect how tightly DNA is packaged. And remember we already said that DNA is packaged too tightly, gene expression won't occur. So this definitely regulates gene expression. So how are histone proteins modified while histone proteins actually have tails? They have these little protein tails that hang off of them. They contain a bunch of different amino acids. But the two important ones are license and argentines and these two amino acids can be modified through a bunch of different ways, most of which we're not talking about. But the two most important ones are through the addition of methyl or acetyl groups. So let's talk about assimilation. First simulation is the addition of acetyl groups and the addition of the Seattle groups results in open chrome aton. So this is what you need to know. You need to be able to connect assimilation with open chrome button. And if the chroma tins open, what does that mean for transcription? Is that going to activate it or suppress it? Right. It's going to activate or promote transcription. Now assimilation is reversible and there are proteins called histone diacetyl. Aces that come in can remove that acetyl group when the acetyl group is gone. What is that going to do with the crow mountain is going to close it back up again and repress transcription. So if you have a settled group, they're a bunch of acetyl groups there. So to open this region of the chromosome is gonna promote that transcription of those genes present there. If the acetyl group is not there it can be closed and if it's closed, that means that transcription of those genes won't occur obvious gene regulation. So the second type is methylation. This is the process of adding methyl groups. Now most often methylation causes closed chroma tin. But notice I said most often because occasionally it can support open chromosome but this is where it gets confusing because some professors want you to just sort of know for the test assimilation causes open methylation causes closed. So I suggest that before you get to a quiz or test that you go to your professor and say, hey does methylation occasionally cause open chroma tin. And what is the answer you're looking for on the test? Because some professors want you to know that there is this most of the time it causes close but can cause open and some of you just some of the professors just say let's make it easy for them assimilation causes open. Methylation causes close. So make sure you know what your professor wants you to believe that methylation does before you get to a test. So um so evolution often causes closed chromosome. Now methylation when it's on there, what it does like the functionality of how this is gonna activate or suppress transcription is when there's a methyl group there that creates a binding site. So other proteins combined to that metal group and then proteins come in and they can either activate or suppress transcription depending on the proteins that are binding to that area. Now obviously there's a bunch of different amino acids, it's not just one licensing and it's not just one. Our ginny his stones are made up of a ton of amino acids and there's a bunch of histone proteins in the nuclear zone. Each one of them have tails. So there's all these huge combinations which we refer to as the histone code now. They so it's the combination of all the histone modifications that affect gene regulation. And I only talked about methylation and methylation but there's actually over 150 different types of modifications that can occur on a histone protein amino acid. And then on top of that there's multiple amino acids. So this this code is huge and we haven't broken it yet. We don't know how to read it yet. And so what kind of what signals cause activation and what signals called suppression is not at all well understood. But there is one pattern that we can say for certain that we know and that's the pattern of CPG islands. So most C. G. Di nucleotides and di nucleotide just means referring to two nucleotides here CNG. So in the genome the majority of these are actually methylated. Sorry if you can hear that siren that's outside. But anyways most of these are methylated. So throughout the entire genome if you have a pair of C. G the majority overwhelming majority you're gonna be methylated. But there are regions of a new methylated C. G. Di nuclear tides and we call these CPG islands. So regions where cogs are not methylated and they're not when they're not methylated. They are very often found in promoter regions. Which makes sense because promoters need to be able to activate genes. So you don't want this methylation occurring in a promoter because that could really cause a closed chroma tin and result in suppression of the gene that the sale may want to actually activate. So here's an example. So here is the new clee zone and each one of these is a different type of histone proteins. And you can see that they have these tails on them. Some of them have won. Some of them have to and as you go along here you can get all different types of combinations right? You can get like this is a lie seen here with assimilation and methylation on it. You have a license up here with just the sea dilation. You have a ton of license and Argenis up here with justice titillation. You have things I didn't talk about including foss for elation. Um The ci one. I don't really know much about the ubiquitous nation that could occur on here. And so all of this all this whole combination here means something this is going to say okay activate this gene or suppress it. Right? But we don't know just by looking at this whether or not this gene would be activated or suppressed. We would have to actually do an experiment to determine that. And so this histone code is a code that scientists are actually currently working on trying to figure out. But you can say it's extremely complex and obviously it's not gonna be easy to figure out. So with that let's quickly get to the third form and that is actually the histone variants. So histone proteins are generally very well conserved. The same histone proteins throughout pretty much every organism, every eukaryotic organism uh even further than that and histone variants are very rare. And what they are is just like their variants right there. Histone proteins but they're not quite the same as the universal histone proteins that are used but generally they're found in unique chromosomal region. So I an example of this is the central mir. Which is always very tightly. I mean just like extremely tightly packaged hetero chroma tin contains their own H. Three. Histone protein variant. So H. Three is just a type of histone protein. And there's a special one found at the centrum here. Why is it? There no one really knows but people suspect that it has something to do with the centrum ear has this very tightly just like abnormally tightly packaged D. N. A. And that that histone variant may play a role in that we don't know for sure but that's just kind of the idea. Um So histone variants are a third way that gene regulation um can be controlled because the center mirror obviously nothing in the center of your location is getting transcribed and that could be potentially due to this histone variant. So with that let's now move on.

Other Chromatin Modifications

Okay, so now we're going to talk about other promoting regulatory mechanisms. So we talked about these sort of like individual amino acids getting modified but actually DNA packaging can cause entire chromosome all effects. So a great example of this, which you're probably already familiar with is X. Inactivation. And so we know that female human females get two copies of the X chromosome. Yeah, we don't need both copies. So one has to become an activated and that inactivated X chromosome is called a bar body. Now that entire chromosomes is inactivated due to hetero crow mountain. And so that's DNA packaging on an entire chromosome level. That shuts off an entire chromosome and prevents all those genes from being transcribed in order to prevent um a huge overdose of gene dosage essentially in females. There's a second term that you're gonna come across and that's genetic imprinting. And what this is is you get one copy of every chromosome from your father and your mother. So one copy will be inherited as an active. So that entire chromosome will be inactive when you inherit it. And depending on which parent it came from, it can either come from the mom or either come from the dad. They'll also have that as an inactive chromosome. And so um pretty much when you get one copy that's an active and one that's active. That means that genes are expressed as if there's only one allele, right? Because if you have one active and one inactive, only this allele on the active chromosome will be expressed. And if that's a recessive, allele that means that the recessive allele is going to be expressed even if the allele on this one was dominant but it's not being expressed so you can't see it. So an example of genetic imprinting is this these mice right here. Aren't they cute? I don't know. I'm not a big mouse fan. But anyways, these are genetically identical mice. If you take their genome and you sequence it, you're going to get the exact same genome between these mice. But they look so different because the one of these mice has has genetic imprinting. So that means one of their chromosomes is entirely inactive. And so that results in genetically identical mice um looking so different because an entire chromosome has now been inactivated and that results in you know, recessive alleles or a single allele showing forth when there should have been two to take over and make them look like each other. So that is genetic imprinting and different ways of entire chromosome chromosome modifications that can affect gene expression. So with that let's now move on.

Chromosomal regions that form heterochromatin contain:

• A. Highly expressed genes
• B. Associations with the nucleolus
• C. Few genes
• D. Lots of open chromatin

Which of the following are examples of epigenetic marks?

• A. Acetylated guanines in DNA
• B. Methylated nucleotides in histone tails
• C. Methylated amino acids in histone tails
• D. All of the above

CpG islands are defined as which of the following?

• A. Highly methlayed CG dinucleotides
• B. Groups of unmethylated CG dinucleotides
• C. Methylated CG dinucleotides found in gene coding regions
• D. CG nucleotides that become methylated to activate the gene

Which of the following terms is associated with closed chromatin?

• A. CpG islands
• B. Heterochromatin
• C. Methylation
• D. Euchromatin