Regulation of Gene Expression Part 1

The topic for today's page is again, insanely complicated - the regulation of gene expression. If there was no gene regulation, cells would constantly print out proteins they don't need and lack any specialty. So, regulation is a must. But how does this work? The answer is very complicated - so much so that I have broken this page into different parts to help you guys understand in little pieces. 

Today, we will be discussing operons and operators, how they are used, examples of them being used, and transcription factors and methods to increase gene expression. Next time, we will talk about DNA bending, transcription factories and alternative spilicing. In the page after that, we will talk about miRNAs, siRNAs, and ncRNAs, and translation regulation.

First, let's discuss operons. Every gene (or group of similar genes) has an a small segment of DNA called an operator that switches it on or off. The state of the operator determines if RNA polymerase is able to transcribe the gene. The operon is the combination of the operator, the promotor (the segment the polymerase binds to) and the genes themselves. So, how do you regulate the transcription of operons? It's quite a complicated process, with many different components. Let's start by discussing the operators, since they control the gene transcription in the first place. The best way to explain how this works is with an example, so let's use the trp operon. The trp operator is on at default, so it can be switched off by a trp repressor protein. Repressors, after binding, do not allow RNA polymerase to bind to and transcribe an operon. Only one specific protein will turn off the trp operator - operons are specific to their genes, and there is only one protein that can turn on or off an operator. The trp repressor protein is created by a regulatory gene (a gene that creates repressors; they are continuously active) called trpR, which has a promotor of its own (even though it is always active at a low rate). 

But if there are always some repressors, shouldn't the gene be off 24/7? Well, that's not exactly how that works - operators can be switched on and then off, or off and then on. The process is reversible, so the operator switches between two states - one where its repressor is attached and one without. And in the case of the trp repressor protein, the protein itself is inactive when it is created. An inactive protein cannot go and shut off an operator. In order to activate it, it must bind to a molecule called trytophan before it can go and shut off the trp operator. In situations like this, we call molecules like trytophan corepressors, which interact with the repressor protein to help switch an operator off. The amazing thing about this process is that controls itself. The trp operon creates tryptophan, but if there is too much tryptophan, it binds to the trp repressor protein which goes and shuts off the trp operator. If there is too little tryptophan, the trp operator turns back on and production starts back up. The duration of a repressor bond increases when there are more active repressors and decreases when there are less. 

Repressors, as I mentioned before, are allosteric (they have an inactive and an active state). They can either be active at default or inactive at default. In the same way, there are repressible operons (operons that are usually on but can be turned off) and inducible operons (operons that are usually off but can be turned on). The trp operson is repressible. Let's discuss an inducible operon to understand how they work as well. The lac operon manages a bunch of genes, one of which is lacZ - a gene that produces an enzyme called β-galactosidase that breaks lactose into glucose and galactase. Usually, a cell only has a few β-galactosidases, but when someone drinks milk, the levels of this enzyme rise rapidly. Let's investigate this.

lac repressors are always active and are thus always repressing their operon. In order to make them let go, you must use an inducer molecule to inactivate it. When lactose is present, the inducer molecule binds to the lac repressor and β-galactosidase is produced to break down the lactose. When lactose is not present, the repressor stays on the operon and β-galactosidase is not produced. Isn't that incredible?

Let's discuss transcription factors next. In order for transcription to start, you need some transcription factors. What are these factors? Transcription factors are... what we just talked about! They are proteins that regulate the expression of genes. Some transcription factors are essential for the production of protein-coding genes, called general transcription factors. Specific transcription factors interact with a specific protein set at a specific time and place. These transcription factors work together and bind to the promotor and create an initiation complex that RNA polymerase binds to before being able to start constructing. I will be discussing transcription factors even more in the page afterward when I explain DNA bending.

Lastly, let's talk about a few ways gene expression is increased. First, when cAMP (a derivative of ATP) binds to CAP (catabolite activator protein), transcription is promoted. When proteins called histones are acetylated, transcription is also promoted. When DNA is methylated (methyl groups are added to a DNA molecule), transcription is ALSO promoted. This is a lot of information, so I will not mention DNA bending (another method of increasing gene expression) in this page - I will discuss it in the next page.

That's all I have for you today! As always, email me at twisha.sharma30@gmail.com if you have any questions at all. Thank you so much for reading and have a great day! I hope to see you in the next one!