Hi in this video we're gonna be talking about transcription regulators of gene expression. So transcription regulators are exactly what they sound like they are things that regulate transcription but how do they work. So transcription regulators control gene expression by either activating or repressing the transcription of genes. So transcription all were pressure repressors um turn off genes and therefore inhibit transcription. And so how they do this is they usually have some type of protein protein interaction with either activators that sort of compete with them for binding or other proteins that stimulate transcription in order to block it. Now transcription activators turn genes on and therefore activate transcription. And generally how transcription activators work is they work with promoters um in order to make them fully functional. So that RNA polymerase combined and then transcribe the gene. Now activators and repressors often don't work alone. They can work with these co activators or co oppressors which also helped to co control transcription. Um And they do this by you know a lot of different ways facilitating transcription through interacting with RNA polymerase or altering chromosome structure or activating regulatory other regulatory proteins. So but they just can help the activator proteins stimulate transcription or inhibit it. And then there's a special type of protein called the mediator which is a big protein complex and it sort of interacts between the regulatory proteins and RNA polymerase to facilitate whatever is going to happen whether that's activation or inhibition. So if we're going to look at this and then back out of the way you can see that we have jeans here in red um and then these promoter regions here and you have an activator bind and that causes transcription. And if you have a repressor bind that blocks blocks transcription and therefore that doesn't happen now in this image. I've shown them working by themselves. So there's there's one activator and one repressor, but in the cell rarely do they ever work alone and require interactions and other proteins to be fully functional. So some of some of these factors are things like transcription factors which can be recruited to the area to regulate gene expression. There are two types of transcription factors that I really want to talk about. These are the general transcription factors and these are the ones binding into the core promoter site. So if you go back to some of our earlier lessons where we talked about transcription, these are the general transcription factors are found in every transcribed gene. Things like T F I H T F I B, you remember back to the video what these do. But then there's also sequence specific factors and these also buying to regulatory sites but generally the proteins that are sequence specific only bind to specific sequences, which makes sense. So you have the general transcription factors which are present any time of genes transcribed and you have specific ones that are recruited only to certain genes because each gene is regulated differently. So if we're to look at what this looks like. Yeah, you guys can still see this image. Um so we have, you know, all these different factors that we've talked about enhancers which can be really far away promoters. We have RNA polymerase, which is going to transcribe the gene. And this here, this blue thing here is the gene and you have all these different transcription factors, activator proteins and variety of different things that activate the transcription of this gene. So they're all working together in combination to promote this activation. Um so not just a single factor. So now let's move on.

So in this video we're going to talk about the DNA binding motifs of transcription regulators that allow them to bind to the DNA. So in order to exert their function, transcription regulators have to be able to interact with the D. N. A. And so there are these really four common DNA binding motifs or regions on these proteins that allow them to interact with the domain. So let's go through each one of these and then I'll show you an example of what they look like. So the first one is the helix turn helix. And um this just means that there's one helix that makes contact with the D. N. A. While the other helix stabilizes the interaction. Um So an example of these that you may read about in your book are things called homo domains which are found on these very crucial developmental genes called hawks genes. Um And they interact with interact with the DNA through helix turn helix. So these are commonly found in these crucial developmental hawks genes. The second one called zinc fingers. And so this one has repeats of sight unseen in history that bind zinc and fold into a finger like structure to bind D. N. A. And I'll show you exactly what this looks like in a second. The third one is gonna be the losing zipper and this actually has two alpha helix sees that dim arise and bind D. N. A. And then we have the helix loop helix which is again to alpha helix is that are connected by a loop that combined D. N. A. So the transcription regulators all have one of these four DNA binding motifs that allow them to interact with the DNA. So it is important to understand what these DNA motifs are, what they look like and how they differ between each other. Now transcription regulators bind to DNA sequences but how long are those? So they can vary quite considerably from 10 to 10,000 nucleotides in length. So these are kind of all over the place. Um and so regulator proteins don't necessarily bind to a single sequence. And that's the only sequence they bind. They can buy into a bunch of different similar sequences meaning that they're degenerate. So they don't need an exact sequence. They just kind of need something similar. Um And they also it's important to realize that when binding the D. N. A. That means they can bind to the nucleotides themselves but they don't have to they can also bind to the backbone or the helix itself and not just the nucleotides but all four of these regions interact with the D. N. A. So here's what they look like. You have your helix turn helix, you have your zinc finger. So here's ink being stored here and some people I guess say this looks like a finger, you have you're losing zipper which I think looks kind of like a zipper. And then you have your helix loop helix where you have your two alpha helix is connected with a loop. So these are your four DNA binding motifs that are really important for transcription regulators. Now pro carry optics use kind of probiotic cells kind of use a different ways to regulate and bind to D. N. A. In order to regulate transcription. So pro periodic issues inter changeable RNA plenary sub units. So remember RNA polymerase is what is driving transcription. And so it controls how it's going to transcribe in, which means it's gonna activate by sort of changing out some of the parts of the RNA plenary. So the part that it changes out is called the sigma subunit. The sigma sub unit is what recognizes a promoter. And so there are many types of sigma subunits, each recognizing a different set of promoters. So if you need to block transcription of something, you just remove the sigma sub unit that recognizes that promoter and put something else in. And so that's how pro carry optic cells control gene expression by replacing the sigma subunits of RNA polymerase. So if we're to look at what this might look like, We have our RNA polymerase here and we have three different sigma factors or you can say sub units, the Blue Wind, the green one and the purple one. And so let's say that the blue one activates or deactivates promoters one through three, The green one does four through six and the purple one does seven through 10. So if you you want to activate gene number five or promoter number five, then you use this sub unit. If you want to activate promoter number 10, use this sub unit, and so pro carry Alex, just interchange these parts in order to activate some jeans and not others. So now let's move on.

So in this video I'm gonna talk about two different kinds of transcription regulators. And those regulators. The two different kinds depend on transcription and regulators that bind um Two sequences located near or far. So those are kind of the two ones that they're buying near to the gene or far away from the gene. So the ones that buy near they buy to a region called promoter proximal elements um that live very near the promoter site. Um And the promoter, in case you need a refresher is where the RNA polymerase binds. And orients it so that it can transcribe the gene. So regulatory factors are all rick to these nearby regions to the promoter proximal elements or the promoter itself to initiate transcription. So if we are looking at what this looks like you would have here your promoter or your promoter proximal elements in your gene and R. N. A. Memories. And so um activators. So your RNA plum rice is going to go here eventually and some other activators will bind to this promoter. The promoter approximate elements in order to transcribe the gene. Now there are other elements and these are regulators that bind to DNA sequences that are far from the gene. So we've gone over a couple of these but I just want to hit them again and maybe add a little bit more information. So enhancers, one of these and so two enhancers, jean activators bind enhancers. They can be upstream or downstream but generally the sort of common thing between enhancers is that they lie thousands of nucleotides away from the gene. Um And how they actually impact the gene is the enhancer causes the D. N. A. To loop between the enhancer and promoter so that the promoter enhancer actually sort of loop around and come in very close contact with each other in order to activate the gene. Now there's this other type called a silencer and this is going to be where gene repressors bind and it acts very similar to an enhancer thousands of nucleotides away upstream or downstream. And it also loops to sort of prevent gene expression. Now if the D. N. A. Can just sort of loop in whatever direction it wants to then enhancers could essentially regulate any gene on a chromosome but we don't necessarily want that to happen. It needs to be more specific than that. So where there there's these reasons called an insulator. You may also see these barrier elements and insulators divide chromosomes into regions so they say okay, you're an enhancer then you can regulate genes that are in within this region. But once you get an insulator, once you reach an insulator you're not going to be able to enhance the transcription of other regions of the chromosome and that provides specificity to enhancers which would otherwise just be able to loop wherever they wanted. Um So we don't really want that. So insulators prevent distant elements. Things like enhancers from acting promoters on a different segment, things that they shouldn't be activating. Now we've talked about a lot of things both near and far but the term that describes the entire DNA sequence involved in regulating the gene is called a gene control region. So that's going to include the promoter promoter proximal elements, insulators, insulators, silencers, enhancers. This entire region that's responsible for regulating the gene. The transcription of the gene is called the gene control region. So the genes control region for this gene that we're looking at which if you remember from the colors above is gonna be here, you have your promoter and you have your enhancer. So this is gonna be the entire gene control region for this gene. And there can be proteins that recruit to the enhancer result in DNA folding. That brings the enhancer close to the nearby genes. And then all of the proteins involved including RNA polymerase are attached on correctly and then that results in gene transcription, which is super important. So now let's move on.

So in this video I'm going to talk about the trip to fan repressor and the lack opteron. And so these are two examples of transcription regulation and prokaryotes, but I think it's really important and you're going to read a lot about it in your textbook. Um so I really just want to take a second to just very briefly go over what these are. So when you're reading about it or hear about it in class, you're not confused. So the trip to fan repressor is when the amino acid trip to fan is acts as a major regulator of gene expression. And so tryptophan actually has the ability to bind to operate ions which are kind of in pro carry optics, stretch called stretches of many related genes. So genes that all can do or have a similar function or kind of work in the same pathway are called an opteron. And tryptophan can actually bind to different ah perons and inhibit transcription. And so for instance um how this works is Tryptophan actually binds to directly binds a transcription a lower pressure and activates the repressor and then that activated repressor then binds to regulatory sequences to inhibit the genes involved in tryptophan creation. So um if there's a lot of tryptophan in the environment then tryptophan is going to bind to a repressor that represses the genes responsible for tryptophan creation. Right? Because there's so much tryptophan in the environment, the cell doesn't need to create trip to fan. So it wants to repress those genes. So that's how the tryptophan repressor works. So um like I said it allows gene expression to be controlled by environmental levels of tryptophan. So when high level of tryptophan there's not going this these genes are going to be um repressed. So how this works is you have this tryptophan repressor and you have tryptophan itself. And so when tryptophan is present, it binds to the repressor and that binds to this opera on here which has a bunch of different genes responsible for trip to fan creation. And so because the tryptophan repressor is binding here, it blocks transcription so that the cell doesn't waste that energy making trips even when it's already available. Now the second one you're gonna read about is the lack operation which is a little bit more complicated. But essentially the lack opera is a bunch of genes that control or regulate lactose in E. Coli. And so there can be so like the trip to fan, the response of this activation or repressing is going to depend on the, you know how much lactose is in the environment. So when there's no lactose available, the lac repressor. So something that's going to repress this halts transcription of the lac opera un so no lactose available, it halts the lack opera. Now if there's glucose available. So this is a different type of sugar but glucose can be used to make lactose, what happens is there's this activator protein called the cap protein. Um but it remains inactive, right? Um But there's no direct repression of the lack opteron. So you have the so you is the lack operation is not being inhibited but it's also not being activated. So it's just kind of existing and there might be low levels of transcription but nothing too big. But with lactose is available. The activator cap binds upstream and actively activates the lack opera on. So here we go. So here we have our lack aPA Ron and we have the cap binding site. So this is gonna be the activator site and then there are three conditions here. So let me back out of the way. So we can say that if there is lactose available, what you're going to see is that the cat protein binds this results in strong expression. If there is, if lactose is unavailable then what happens is the cat protein doesn't bind and therefore RNA polymerase doesn't bind. And so these black genes are not expressed but you have this kind of third option here. Whereas if lactose is low but there's this high amount of glucose. So there's you know, just this high amount of glucose. What happens is the cat protein is activated but it doesn't really do anything. So you don't get RNA plum race, it's not really binding here. And so what you get is just very low levels of gene expression of this opera on. So that is how the lack opera on and the trip to Fan Professor work. So hopefully that was clear feel free to re watch these videos if you need to. But now let's turn the page.