 Today's topic is gene regulation. Every somatic cell in an organism contains identical genetic instructions. But liver cells, immune cells, nerve cells, muscle cells, they all look and behave quite differently. So what makes them so different? The answer is gene regulation. Similar to people in school, when you start off in elementary school, you can be anything you want. Maybe a policeman, lawyer, doctor, anything. And then in high school, you begin to focus on certain subjects that you like, kind of narrowing down the fields that you're interested in. And then in college, you choose a specific career path. So you become very specialized when you take these different paths. Cells can also become specialized or differentiated. They can turn certain genes off, they can turn others on, and they can affect the cell's appearance and function. So again, cells can have absolutely identical DNA, but depending on which genes are turned on and which genes are turned off, they can appear and function very differently. So let's first start by talking about gene regulation and bacteria. So natural selection tends to favor bacteria that express only certain kinds of genes, only at specific times whenever the products are needed by the cell. So for example, if you guys came home and there was a three-course meal ready and sitting on the kitchen table, would you pull out a pan and start making ramen noodles? No, you already got food ready. Or if you were an accountant, would you buy three microscopes and a pH meter? No, probably not. It's not something that you need for your particular job. Same thing with the cells. So how do bacteria selectively turn their genes on or turn their genes off? One way is by using the operon system. So an operon includes a cluster of genes with related functions, and they have one regulatory sequence that turns the entire group on or turns the entire group off. So it's a little bit like a traffic light. So the traffic light can turn red, yellow, and green, and depending on what color that light is, you know, you can have a series of cars in line that are either allowed to go when it's green or stop when it's red. Same exact thing with an operon. So we've got gene one, gene two, and gene three, and they have a regulatory sequence that tells them to either be completely on or completely off. So E. coli uses an operon that's called the LAC operon or the lactose operon. This regulates a group of genes involved in the breakdown of lactose. So when no lactose is present, the genes are turned off to save materials, to save energy. But when you drink a milkshake, the bacteria in your gut turn on lactose digestion genes so they can also enjoy that milkshake as well. Now the LAC operon involves three parts, a promoter, an operator, and a repressor protein. Now a promoter is simply a DNA sequence where the RNA polymerase binds and initiates transcription. An operator is also a DNA sequence, but this operator acts as an on or off switch. And then we have a repressor protein which binds to the operator and physically blocks the RNA polymerase. So down here we've got the promoter, we've got the operator, and got genes maybe one, two, and three. And then we have a repressor protein. If the repressor protein binds, it blocks the ability of the RNA polymerase to do transcription. So it's physically blocked. And so genes one, two, and three are off. So just to drive home that point again, a repressor protein physically blocks transcription. So if you've got a grizzly bear, if you've got a big guy with an axe or a hammer, if you've got an ox, it physically blocks that RNA polymerase from doing its job. So those genes aren't going anywhere. Those genes are off inactive. But when milk sugars are present, lactose can bind to the repressor protein and change its shape. Then the repressor protein can no longer bind the operator. And then the RNA polymerase can happily bind the promoter. And genes one, two, and three can be transcribed. So again, we've got this little molecule of lactose. It can bind to the repressor protein changing its shape. Now it can no longer bind to that operator sequence. And so since it can no longer bind, it goes away. And now RNA polymerase can bind the promoter. And then we can get transcription of genes one, two, and three. Now once all of the milk sugars are digested and gone, lactose is no longer binding that repressor protein. So now that repressor protein can once again bind the operator. This physically blocks the RNA polymerase. And so no gene transcription takes place. So again, the repressor protein comes and physically blocks the RNA polymerase from being able to go on to do gene transcription. Now gene regulation can also involve DNA packing, transcription, translation, and post-translational modifications. So just to kind of drive home the point, there are many places where gene can be turned off. So if transcription or translation are stopped, or if the products of transcription or translation are broken down, you will never see the final product of that gene, and you will not have the particular phenotype of that protein. So here's an example of what I'm talking about with DNA packing. So first we start off with naked DNA, double-stranded DNA. And that double-stranded DNA can wrap around proteins, and particular histone proteins. And so this simple structure where DNA is wrapping around those histone proteins is the first level of DNA packing, and that's called the nucleosome. And you can see down here, another picture of it, where in this case the DNA is wrapping twice around those proteins. So the more wrapped up the DNA is, the harder it is for RNA polymerase and other enzymes to access it. Now that DNA packing can get even more tightly packed. So if you've got a large group of nucleosomes, these guys can coil together and become more tightly packed. And then you can also have supercoiled DNA, even more tightly packed in the form of chromosomes. Now again, the more the DNA is condensed or more tightly it's packed, the harder it is to access by enzymes like RNA polymerase. So the tighter it's packed, the more likely those genes will be turned off. So it's kind of like you throw a bunch of items into a box, and it's easy to find, look into the box, pull out a frying pan, look into the box, pull out a shower curtain. Now, if you had bubble wrapped all of those items, if you had taped up that box and you had shoved it in the top of your attic, it would be very difficult to find an access like maybe your coffee pot. The exact same thing is happening with the DNA. So again, the more the DNA is condensed or tightly packed, the harder it is to access by those enzymes and the gene is turned off. So one way that this DNA packing can be controlled is by chemical modifications or epigenetics. So two different types of chemical modifications can take place, methylation and acetylation. So methylation is where you add a CH3 group to either the DNA or the histones. And acetylation can take place on histones where you add this particular chemical moiety. Now again, the sequence of the DNA is absolutely the same, so we haven't mutated it at all. But the DNA packing has changed. So in some cases these modifications will cause the DNA to be more relaxed or looser, and so those genes might be more likely to be turned on. In other cases these modifications make the DNA more condensed, more tight, so those genes are much more likely to be turned off. So this can affect single gene, this can affect a region of genes, or this can affect the entire chromosome. And one example of that last case is X chromosome inactivation. So gentlemen, your sex chromosomes are an X and a Y. Ladies, your chromosomes are two X's. Now the body needs a way to only have a certain amount of gene expression. So males have one copy of X chromosomes, but females don't want twice as much gene products, so they need a way to control that gene regulation. And so in females one of those X chromosomes is randomly inactivated or very very tightly condensed. So you can see down here we've got two chromosomes, and one of them is very very condensed, tightly bound, and it forms what's called a bar body. And so that DNA is shut off. So here's an example where we've got two chromosomes. One of these chromosomes has a gene for an orange protein. This chromosome, the box isn't there, but it shows a chromosome that has a black gene copy. And over here, again, that X inactivation is absolutely random. So in this case this chromosome formed a bar body, so its genes are off. So the cell in this particular case will have that orange color. Now one example of this is with calico cats. So you can have two female cats with exactly the same DNA, identical DNA, but these cats can look very different, because again that X inactivation is absolutely random. So here we've got a kitty with a lot of black in its face, and over here we've got a cat with a lot more orange. So again, they can have the exact same DNA, but because of how that DNA is packed, you can have different gene expression.