When I was a little kid, I had this art teacher. She had Ms. Frizzle energy – and a room full of art. And one of her favorite things to say was, “You’ve got to express yourself; art is a way you express yourself. In the art.” I had her all through elementary, she started saying this when I was like 7 and the phrase didn’t have much meaning for me at first. She told us music was another way – and dance – I wasn’t really into those either. It wasn’t till a lot later I got into poetry which I love. That was my creative expression; my mitosis poem will catch on someday. Anyway, the word “express” stuck with me. As a kid, I understood it that it was a way to take the creativity we all have inside of us and let it out. But that’s creative expression. Our cells have expression, too. Gene expression. They can express genes. To express a gene means that a gene can be used to make something functional, often a protein. In our protein synthesis video, we talk about those steps: the gene – which is made up of DNA – can be transcribed into mRNA during transcription and then used in translation to make a polypeptide chain. A protein is made up of 1 or more of those chains. But you know what? It’s not doing that with every single gene. Not every gene is expressed. That’s why the phrase gene regulation gets put with gene expression because the expression has to be regulated. A cell in the eye has no need for using a gene that codes for stomach acid even though the gene is present. It would be wasteful to express that gene. And likely uncomfortable. Prokaryotic cells and eukaryotic cells both have genes to express. Some differences, though. Recall that prokaryotic cells just have the DNA in their cytoplasm; they don’t have a nucleus. So, transcription and translation all just happen here; unlike in a eukaryotic cell, there’s no traveling of the DNA out of a nucleus. Nope, in prokaryotes, it’s all right there together and can really both be happening together at the same time as there’s no nucleus involved. For prokaryotes, a lot of the control of whether a gene is going to get expressed or not directly tends to involve or impact transcription. Eukaryotes also have gene regulation that involves transcription although they’ll have a lot of other points for gene regulation too that we’ll get into soon. So you might wonder, how does gene regulation involve or impact transcription? Transcription again is when an enzyme called RNA polymerase makes mRNA from a DNA template. There are regulatory proteins that can decrease or increase transcription and that’s important among both prokaryotes and eukaryotes. These regulatory proteins are often referred to as transcription factors. In eukaryotic cells, a variety of these factors are usually needed. Some transcription factors bind to a DNA region called the promoter to help RNA polymerase start transcription, while other transcription factors can bind there to repress it. Some types of transcription factors can bind to enhancer sequences, where they increase transcription and enhancer sequences can even be far away from the gene. Some transcription factors or other proteins can bend the DNA to bring the promoter and enhancer closer. Ultimately, transcription factors play huge roles in whether a gene is expressed and we also want to mention, environmental factors can influence transcription factors, meaning that the presence or absence of an environmental factor could impact gene expression. Prokaryotes commonly have operons which feature a regulated cluster of genes along with a promoter and an operator, and they make great examples of gene regulation during transcription. We have an example of this in our Order of the Operon video, but here’s a quick recap of just one type of operon known as the Lac Operon. Here is a repressor. The repressor blocks RNA polymerase from doing transcription and it does this by binding to a sequence called the operator. Since the RNA Polymerase can’t work, ultimately this genes are not going to get expressed. That’s because the genes are not going to be transcribed into mRNA so it will not go to translation for a protein to be built. And that’s great when the protein isn’t needed. This is how the bacterium is regulating the genes in this operon. But sometimes, the bacterium may need these genes expressed. And that’s because these genes code for specific proteins, including an enzyme that breaks down a sugar called lactose. So, when lactose is around, the bacterium wants that enzyme because it wants to break the sugar lactose down: it can eat the broken down lactose. So how does the bacterium turn a gene “on” – how does the gene get expressed? Well, as you can imagine, this repressor has got to be moved; it’s in the way of transcription happening. And it turns out, a form of lactose, technically an isomer of it - binds to the repressor which makes it get out of the way. When the repressor is not blocking this RNA polymerase, transcription can happen. The RNA polymerase does transcription and it makes the mRNA. And translation can follow and it uses that mRNA to make: protein! Which, includes an enzyme that can break down lactose and other proteins too involving lactose. So these genes are being expressed when lactose is around. Expression of that gene is not happening when lactose isn’t around. It’s a gene regulation example: controlling whether genes are expressed or not. And still on the subject of gene regulation that can impact transcription, we want to mention from our epigenetics video that there can be epigenetic marks on DNA that can ultimately impact transcription . Eukaryotic DNA is often packed by winding the DNA around proteins called histones. There are chemical groups - like methyl - for example, that can influence how tightly that DNA is packed. If the DNA is really tightly packed, transcription factors can’t really bind in there very well. So, if those factors can’t bind, then transcription doesn’t happen as shown here with this highly methylated area. But in this case, if methyl is removed, that would then allow the DNA to be transcribed and eventually be used to make protein. So, it could then be expressed. And just a note: this can also occur in prokaryotes although there are differences: for example, in the DNA packing. Now, remember we said that prokaryotic cells tend to have most of their gene regulation focused around transcription. Eukaryotic cells, however, tend to have more potential opportunities for gene regulation: for example, it’s also common for eukaryotes to have gene regulation that is post-transcription but before translation, during translation, and even post-translation. Let’s have an example of eukaryotic gene regulation that is post-transcription but before translation. So let’s say, an mRNA was made in transcription. Eukaryotic cells tend to do significant processing of the mRNA afterwards and certain areas of the RNA are actually removed. Introns are RNA portions that are removed. This is a type of regulation, because if they’re cut out then they’re not going to be expressed, but also, it can impact the portions that remain. The portions that remain are called exons and those portions will go on to translation. Let’s have an example of eukaryotic gene regulation that impacts translation. So remember for translation you have the mRNA, you got the ribosome, and you got the tRNAs. So there’s a little protein called eIF-2, or its fancier name, eukaryotic initiation factor-2. Its job? Well, it helps translation get started, hence the initiation. Important for ultimately making a protein. But eIF-2 itself can be regulated. If eIF-2 is phosphorylated – which means it has a phosphate group added to it - that makes its shape change so it can’t do any initiating. No initiation means no translation. So, no protein made. The gene is not expressed. Finally, there’s even post-translation regulation, meaning it comes after translation. Chemical groups can be added to proteins or removed from them which can change where they end up located or how they function, therefore impacting their expression. Like we mentioned for transcription, environmental factors like limited nutrients or UV exposure can influence those modifications. And then there’s also ubiquitin. Attach that to a protein and that can signal the protein to be degraded so that’s going to affect expression, too. Let’s recap all we’ve talked about. We mentioned what gene expression is: it’s when a gene is used to make a product which is often a protein. We talked about how gene regulation is a related term as many times, whether a gene is expressed or not is often something that can be controlled or regulated. Prokaryotic cells tend to have gene regulation mechanisms that impact transcription; we talked a bit about an operon as it makes a great example. Eukaryotic cells can have gene regulation during or impacting many potential points including transcription but also post-transcription, translation, post-translation – and we gave a few examples. So why does this matter? Well not only does it really matter for understanding how genes in our bodies are expressed, but gene expression is also important to understand when cells in the body are not functioning correctly. Cancer cells, which we’ve talked about before, can have genes expressed that should not be or not have certain genes expressed that should be. One example is a cancer cell with a mutation that increases transcription factor activity. If this boosts the transcription of genes that speed up cell division, it could contribute to cancer cells dividing over and over. Gene regulation and gene expression are very important to developing treatments for many conditions. Well, that’s it for the Amoeba Sisters, and we remind you to stay curious!