Action of Transcriptional Regulators - Online Tutor, Practice Problems & Exam Prep

Combinatorial Control

Hi. In this video, I'm going to be talking about the action of transcription regulators. So the first kind of action that I want to talk about is the fact that transcriptional regulators work in combination with other proteins. Now, I've already mentioned this in previous videos, but I really just want to add an extra layer of what I mean and how this whole entire process works. So combinations of regulator proteins work together to regulate or control (whichever one you prefer) gene expression. So what this means is that multiple proteins work together to control the expression of a single gene. So, usually how this works is there is a single protein that binds first. And, this protein has a really high affinity, or sort of binds strongly to whatever element it's binding to. And then, this binding sort of changes configurations or recruits other proteins and increases the affinity of all of these other proteins that as they get added on, sort of bind more strongly. And, really, the function of this is to limit the number of transcription regulators needed, because if they all sort of bound very weakly, you would need a lot of them to exert some kind of function. Whereas, if the affinity is constantly being increased with each one, they're binding strongly, they can have a stronger function. However, expression can be decided by a single regulatory protein, meaning that this would be kind of like an on-off switch. So you have say 20 proteins there, and the 21st one is really what pushes it to stimulate. So, if you never get the 21st protein to get to the correct area, or bind to the correct things, then even if all other 20 proteins are there and ready to go, it needs the 21st to really get started. So turn that switch on and off. Now, the same combinations can control the generation of different cell types. So, there are a few transcription factors or transcription regulators that control sets of genes involved in cell differentiation. So, say you have your 20 gene regulators, and they are all responsible for creating a kidney cell. And so, these regulators all control most of the genes responsible for differentiating a cell into a kidney cell. So, combinations can work on different genes. It's not just every gene has a different combination, but, sets of genes can have similar ones, especially those that result in cell differentiation. And then also, combinations can be controlled by environmental signals. So, response elements, for instance, are DNA sequences in a promoter that bind to regulatory proteins, but response elements bind to regulatory proteins that are stimulated by kind of external signals. So for instance, you might read about heat shock response elements, which respond when the cell is in temperatures that are really high, or different hormones act this way. So hormone signals can activate response elements, and so these are all external signals that can work to regulate the transcription of a gene. So, here we have an example of sort of combinations. You have your RNA polymerase. You have your promoter region here. You can kind of see this little green. You have all these different regulators, and all that support and work together to support the transcription of a gene. So combinations are really important. So now let's move on.

Gene Activation

So, in this video, I'm going to be walking through the steps of gene activation. So, remember, cell biology likes to do a lot of different steps. We're going to be memorizing a lot of steps, a lot of pathways, and so this is the pathway for gene activation. So, first though, so first what happens is regulatory proteins bind to an enhancer. And, then this binding stimulates the DNA to form a loop, which connects the enhancer and the promoter. Once the enhancer and promoter are together, activators come in, interact with coactivators to alter chromatin structure. The chromatin structure allows for the loosening of the chromatin. And, these activators also interact with a protein known as a mediator. And, the mediator facilitates the correct positioning of RNA polymerase, and then RNA polymerase can start transcribing. So, if we're looking at what this looks like, I've sort of notated here each step. Step. So in step 1, the enhancer is bound. In step 2, this sort of recruits, this, loop here, where the enhancer and the promoter can interact. In step 3, different types of other activators are recruited. Step 4 is when the mediator helps facilitate the interaction between these activators and RNA polymerase. RNA polymerase then comes in, and then finally, in step 6, the gene is transcribed. So those are the 6 steps to gene activation. So now let's move on.

Nuclear Receptors and Hormones

So in this video, I'm going to be talking about a really important class of transcriptional regulators, and that is nuclear receptors. Nuclear receptors are transcriptional regulators that are responsible for sensing hormones, things like steroids, and then regulating gene expression based on hormones. Nuclear receptors contain a few important structures. One is that there's an N-terminal domain, and this is a sort of an activation domain. This is really what's activated by the hormone. And then there's a second structure, a DNA binding domain, which is going to interact with the DNA and then support some type of transcriptional regulation.

Nuclear receptors also have things known as inverted repeats, which are sequences of nucleotides, that are followed downstream of something down, later downstream by a kind of reverse complement. A reverse complement is a fancy term that we use in genetics a lot to actually talk about the sequence of the gene. But the inverted repeat is exactly what it sounds like. It's just kind of a reverse of a reverse sequence of the one upstream. Nuclear receptors contain a lot of these. And the nuclear receptor itself binds a region of DNA called the hormone response elements. These are going to be inverted repeats that many nuclear receptors find.

Here's an example of hormone activation. Now, there's a lot of fancy things here you don't need to know about. Just realize that outside a variety of things to activate transcription and a variety of things to activate transcription, transcription eventually results in the development of a protein and some kind of change in cell function in response to the hormone itself. So this is how hormones work. So now let's move on.

Choose all of the following factors involved in combinatorial control of gene expression.

a) Regulatory proteins

b) Response elements

c) Histone Proteins

d) RNA polymerase

e) Glycosylation

So this question asks you to choose all of the following factors involved in combinatorial control of gene expression. So, if any factors here, (a, b, c, d, or e) are involved in the regulation of gene expression, they are correct answers. There could be more than one correct answer here. So, take a second and see which ones do you think are involved in regulation of gene expression? Regulatory proteins, response elements, histone proteins, RNA polymerase, and glycosylation. Okay. So, now, let's go through each of these and see if we can figure it out. A says regulatory proteins. Well, this one is kind of simple; regulatory proteins are really involved in the regulation of gene expression of some kind. So, (a) is definitely a factor. B says response elements. Now, if you remember, response elements are associated with nuclear receptors and hormones that definitely affect gene expression. So, (b) is an answer. C mentions histone proteins. Now, don't get confused by this answer because it isn't saying histone protein modifications. It's not saying methylation. It's not saying acetylation. It's just saying histone proteins. Now histone proteins by themselves are just proteins attached to DNA and have nothing to do with gene expression directly. It's the modifications added to histone proteins that have things to do with gene expression. So (c) is not an answer. D mentions RNA polymerase. Well, RNA polymerase, of course, is involved in transcription and hence in gene expression. So, (d) is definitely an answer. E mentions glycosylation, so what do you think? Is glycosylation really important for control of gene expression? No. Glycosylation is an entirely different process, so (e) is definitely not it. So the answers to this question are (a), (b), and (d). So now, let's move on.

What are nuclear receptors?

• A. Hormones
• B. Receptors found on the surface of the nucleus
• C. Receptors found on the surface of the cell
• D. Proteins in the nucleus that bind to hormones

Here’s what students ask on this topic:

What are transcriptional regulators and how do they function in gene expression?

Transcriptional regulators are proteins that control the rate of gene expression by binding to specific DNA sequences. They function by interacting with enhancers and promoters, forming loops that facilitate the recruitment of RNA polymerase. These regulators often work in combinations, enhancing the affinity of proteins involved in gene activation. This process involves several steps: binding of regulatory proteins to enhancers, chromatin remodeling to loosen DNA, and positioning of RNA polymerase at the promoter. Environmental signals can influence these combinations, impacting cell differentiation and gene expression in response to various stimuli.

How do nuclear receptors regulate gene expression?

Nuclear receptors are a class of transcriptional regulators that sense hormones, such as steroids, and regulate gene expression based on these signals. They contain an N-terminal activation domain and a DNA-binding domain. Upon hormone binding, the nuclear receptor undergoes a conformational change, allowing it to bind to specific DNA sequences called hormone response elements, which often contain inverted repeats. This binding facilitates the recruitment of co-activators and RNA polymerase, leading to the transcription of target genes. The process ultimately results in the production of proteins that alter cell function in response to the hormone.

What are the steps involved in gene activation by transcriptional regulators?

The steps involved in gene activation by transcriptional regulators are as follows: 1) Regulatory proteins bind to an enhancer. 2) This binding stimulates the DNA to form a loop, connecting the enhancer and the promoter. 3) Activators are recruited and interact with co-activators to alter chromatin structure, loosening it. 4) Activators also interact with a mediator protein, which facilitates the correct positioning of RNA polymerase. 5) RNA polymerase is recruited to the promoter. 6) RNA polymerase initiates transcription of the gene. These steps ensure precise control of gene expression in response to various signals.

How do environmental signals influence transcriptional regulation?

Environmental signals influence transcriptional regulation through response elements in the DNA. These response elements are specific sequences in the promoter region that bind to regulatory proteins activated by external stimuli. For example, heat shock response elements respond to high temperatures, while hormone response elements respond to hormonal signals. When these environmental signals are detected, they activate the corresponding regulatory proteins, which then bind to the response elements. This binding can recruit other proteins, such as co-activators and RNA polymerase, leading to changes in gene expression that help the cell adapt to the environmental conditions.

What role do combinations of transcriptional regulators play in cell differentiation?

Combinations of transcriptional regulators play a crucial role in cell differentiation by controlling the expression of sets of genes involved in this process. Multiple regulators work together to ensure that specific genes are activated or repressed at the right time and place, leading to the development of specialized cell types. For example, a combination of 20 gene regulators might be responsible for differentiating a cell into a kidney cell. These combinations can be influenced by environmental signals, ensuring that cells respond appropriately to external cues and differentiate correctly. This coordinated regulation is essential for the proper development and function of multicellular organisms.