Negative and positive control of gene

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m25

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I've come across two different definitions of negative and positive control of gene, and I'm not sure which one is the right one. The first one says:

"Positive control is accomplished by inducible systems, in which a repressor is removed from the operon by the inducer to promote transcription of a gene. Negative control is accomplished by repressible systems, in which a repressor–corepressor complex binds to the operon to prevent transcription. "

and another one says:

"Negative control is when gene is regulated by absence/presence of repressor, while a positive control is when a gene is regulated by absence/presence of an activator."

Which definition is right? and is lac operon an example of negative or positive control? Please help, I've looked all through online and MCAT study materials but they don't seem to agree at all and I'm confused.

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The lac operon uses both positive and negative regulation.

The repressor protein binding to the operator region is an example of negative control.

CAP (catabolite activator protein) binds upstream of the operator region when it is activated with high lactose levels.

I think your second definition is a little easier to work with. Repressors are involved in negative control and activators are involved in positive control.
 
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The lac operon uses both positive and negative regulation.

The repressor protein binding to the operator region is an example of negative control.

CAP (catabolite activator protein) binds upstream of the operator region when it is activated with high lactose levels.

I think your second definition is a little easier to work with. Repressors are involved in negative control and activators are involved in positive control.
What do you mean by the lac operon using both positive and negative regulation?
So both definitions are technically correct?
 
I mean the lac operon has both positive and negative controls, as I stated.

Yes, both definitions are correct.
 
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Great response by Cawolf. I thought I would add some additional insight since this is something I once struggled with myself.

The terminology can lead to some confusion. Two classic examples given to explain this topic: the lac operon and trp operon. The lac operon is involved in metabolizing the sugar lactose when glucose levels are depleted. To avoid wasting energy, we ensure that this system remains in its OFF state and is only turned on when needed. Therefore, it's an inducible system. On the other hand, the Trp Operon is involved in producing tryptophan, one of the 20 aminoacids. When we have an excess supply of tryptophan, this system is turned off via negative feedback and therefore, we refer to it as a repressible system. Both of these examples refer to negative control, because in each scenario, the active form of the repressor binds to the operon and turns transcription off.

However, the lac operon also is involved in positive control; that is, it can increase transcription activity. When glucose levels drop, the cytosol of the bacteria has a large amount of cAMP (which indicates low energy status). This molecule binds to another molecular called CAP, which together increases the affinity of RNA polymerase to bind to the operon and begin transcription. To reiterate, this binding of the CAP-cAMP complex is referred to as positive control because it increases the amount of transcriptional product produced.

What's interesting is that both positive and negative control are apparently necessary for the lac operon to work adequately. That is, we must have high levels of lactose to promote the removal of the active form of the repressor, but also high levels of cAMP (which binds to CAP), since RNA polymerase requires CAP-cAMP to be bound in order to produce sufficient quantities of the mRNA product. This ensures that lactose is only metabolized when glucose levels are low, and that glucose is the primary energy source when available.
 
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I mean the lac operon has both positive and negative controls, as I stated.

Yes, both definitions are correct.
Great response by Cawolf. I thought I would add some additional insight since this is something I once struggled with myself.

The terminology can lead to some confusion. Two classic examples given to explain this topic: the lac operon and trp operon. The lac operon is involved in metabolizing the sugar lactose when glucose levels are depleted. To avoid wasting energy, we ensure that this system remains in its OFF state and is only turned on when needed. Therefore, it's an inducible system. On the other hand, the Trp Operon is involved in producing tryptophan, one of the 20 aminoacids. When we have an excess supply of tryptophan, this system is turned off via negative feedback and therefore, we refer to it as a repressible system. Both of these examples refer to negative control, because in each scenario, the active form of the repressor binds to the operon and turns transcription off.

However, the lac operon also is involved in positive control; that is, it can increase transcription activity. When glucose levels drop, the cytosol of the bacteria has a large amount of cAMP (which indicates low energy status). This molecule binds to another molecular called CAP, which together increases the affinity of RNA polymerase to bind to the operon and begin transcription. To reiterate, this binding of the CAP-cAMP complex is referred to as positive control because it increases the amount of transcriptional product produced.

What's interesting is that both positive and negative control are apparently necessary for the lac operon to work adequately. That is, we must have high levels of lactose to promote the removal of the active form of the repressor, but also high levels of cAMP (which binds to CAP), since RNA polymerase requires CAP-cAMP to be bound in order to produce sufficient quantities of the mRNA product. This ensures that lactose is only metabolized when glucose levels are low, and that glucose is the primary energy source when available.

So is an inducible system one in which the transcription is normally turned off by a repressor, and repressible system a gene that is normally turned on by presence of activator? Or is it vice versa? I'm confused.

So in the lac operon, the active form of the repressor (that is inhibited upon the binding of lactose) is an example of negative control because the gene is regulated by a presence/absence of a repressor, and the CAP-cAMP is an example of a positive control because CAP-cAMP acts as an activator?
 
So is an inducible system one in which the transcription is normally turned off by a repressor, and repressible system a gene that is normally turned on by presence of activator? Or is it vice versa? I'm confused.

So in the lac operon, the active form of the repressor (that is inhibited upon the binding of lactose) is an example of negative control because the gene is regulated by a presence/absence of a repressor, and the CAP-cAMP is an example of a positive control because CAP-cAMP acts as an activator?
A more simple way to put it:

Lac operon is usually OFF but can be turned ON when needed = this is an inducible system; usually catabolic (break down) systems operate this way.
Trp operon is usually ON but can be turned OFF when needed = this is a repressible system; usually anabolic (build up) systems operate this way.

Postive control = refers to activators (when actively bound, increases transcription activity).
Negative control = refers to repressors (when actively bound, decreases transcription activity).
 
A more simple way to put it:

Lac operon is usually OFF but can be turned ON when needed = this is an inducible system; usually catabolic (break down) systems operate this way.
Trp operon is usually ON but can be turned OFF when needed = this is a repressible system; usually anabolic (build up) systems operate this way.

Postive control = refers to activators (when actively bound, increases transcription activity).
Negative control = refers to repressors (when actively bound, decreases transcription activity).

I see, but how do these relate to the definition below?

"Positive control is accomplished by inducible systems, in which a repressor is removed from the operon by the inducer to promote transcription of a gene. Negative control is accomplished by repressible systems, in which a repressor–corepressor complex binds to the operon to prevent transcription. "

According to this definition, it seems as if repressor regulates both positive and negative control. And what the heck is a "repressor–corepressor complex" in a negative control?

Also, are all inducible system also positive control, and are all repressible system also negative control?
 
I see, but how do these relate to the definition below?

The way they are presenting it is leading to a lot of confusion, because they are referring to the operon activity:

anything that turns ON transcription = positive control
anything that turns OFF transcription = negative control

More appropriately, and the way its more commonly taught is through the perspective of protein activity (activators or repressors):


activators (increase transcription activity) = positive control
repressors (decrease transcription acitvity) = negative control

---

But if you prefer to use their outlook, maybe this might help clarify what they mean...


"Positive control is accomplished by inducible systems, in which a repressor is removed from the operon by the inducer to promote transcription of a gene."

Again using the lac operon as our example (an inducible system). Here the inducer is allolactose. The repressor (naturally active) is bound to the operator. Once allolactose increases and then binds to the active repressor, the repressor-inducer complex becomes inactive and is no longer able to bind. This in turn, turns transcription ON.

"Negative control is accomplished by repressible systems, in which a repressor–corepressor complex binds to the operon to prevent transcription. "

Trp operon is a repressible system. In this scenario, the repressor is normally inactive. However, once the corepressor (Trp aminoacid) binds to the the inactive repressor, it's now able to bind to the operon. This in turn, turns transcription OFF.
 
Again using the lac operon as our example (an inducible system). Here the inducer is allolactose. The repressor (naturally active) is bound to the operator. Once allolactose increases and then binds to the active repressor, the repressor-inducer complex becomes inactive and is no longer able to bind. This in turn, turns transcription ON.
So are you saying that the inducer allolactose is acting as the activator here? But I thought activator binds directly to the gene (usually on its promoter site) it's regulating and not to the repressor...? Or is anything that turns on the transcription termed as activator, no matter where it binds?

So can we say that
activators (increase transcription activity) = positive control=> found in inducible system(since activators induce gene transcription)
repressors (decrease transcription acitvity) = negative control=> found in repressible system (since repressors repress gene transcription)
 
So are you saying that the inducer allolactose is acting as the activator here? But I thought activator binds directly to the gene (usually on its promoter site) it's regulating and not to the repressor...? Or is anything that turns on the transcription termed as activator, no matter where it binds?

So can we say that
activators (increase transcription activity) = positive control=> found in inducible system(since activators induce gene transcription)
repressors (decrease transcription acitvity) = negative control=> found in repressible system (since repressors repress gene transcription)
The inducer (allolactose) associated with lac operon and the corepressor (trp aa) associated with trp operon are both simple molecules that act on the repressor. Do not confuse this with an activator, which is entirely different. Like you said, activators act directly on the dsDNA. It's also worth noting that the repressor itself, as well as activators (ie. CAP) are both proteins, somewhat analagous to transcription factors in Eukaryotes.

Personally, I would ignore their definition and focus on the one Cawolf and me are presenting. I've never seen it presented any other way. The resource you're using seems to be unnecessarily confusing. And for what it's worth, this topic is rarely presented on exams and is such a low-yield topic, so while it's good to understand the basic function of an operon and how it can be regulated, this extensive detail is unnecessary for the MCAT.
 
The inducer (allolactose) associated with lac operon and the corepressor (trp aa) associated with trp operon are both simple molecules that act on the repressor. Do not confuse this with an activator, which is entirely different. Like you said, activators act directly on the dsDNA. It's also worth noting that the repressor itself, as well as activators (ie. CAP) are both proteins, somewhat analagous to transcription factors in Eukaryotes.

Personally, I would ignore their definition and focus on the one Cawolf and me are presenting. I've never seen it presented any other way. The resource you're using seems to be unnecessarily confusing. And for what it's worth, this topic is rarely presented on exams and is such a low-yield topic, so while it's good to understand the basic function of an operon and how it can be regulated, this extensive detail is unnecessary for the MCAT.
Oh okay, so the presence of an activator is not an absolute necessity in a positive control as inducer can activate the gene instead?
Yeah, I guess(and hope) the new MCAT won't go into this much detail, but I'm just curious.
 
Oh okay, so the presence of an activator is not an absolute necessity in a positive control as inducer can activate the gene instead?
Yeah, I guess(and hope) the new MCAT won't go into this much detail, but I'm just curious.
The term inducer and corepressor refer to the molecules that influence the repressor (either switch it on/off). Activators function separately and are influenced by other molecules. I gave the example of cAMP binding to CAP. The terms aren't so important as understanding what they do and how they influence the systems.

Despite the confusing terminology, what these molecules (cAMP, allolactose, trp) all have in common is that they essentially act as switches to turn the protein ON/OFF (repressor or activator). We can further label the operon based on how these regulated processes influence gene activity: if the operon is normally OFF but turned ON= inducible system; if it goes from ON to OFF = repressible system.

Positive vs. Negative Control refer to the presence of either a bound activator (+ effect on the operon; increases transcription ... provided repressor isn't blocking) vs. a bound repressor (- effect on operon; prevents transcription).

-------

Here's an analogy that might help. Consider a dimmer switch, the one where you can twist the wheel to make the light brighter and click it, to turn it on or off. Basically, the activator acts in a similar way to turning the switch (making the light more bright). This is analagous to increasing transcription. Likewise, a repressor bound is like turning off the light. Regardless of how we turn the wheel, if the light is off (repressor is bound), then nothing will happen (transcription won't proceed).

This resource might help visualize the process better: http://www.phschool.com/science/biology_place/biocoach/lacoperon/effect.html
 
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The term inducer and corepressor refer to the molecules that influence the repressor (either switch it on/off). Activators function separately and are influenced by other molecules. I gave the example of cAMP binding to CAP. The terms aren't so important as understanding what they do and how they influence the systems.

Despite the confusing terminology, what these molecules (cAMP, allolactose, trp) all have in common is that they essentially act as switches to turn the protein ON/OFF (repressor or activator). We can further label the operon based on how these regulated processes influence gene activity: if the operon is normally OFF but turned ON= inducible system; if it goes from ON to OFF = repressible system.

Positive vs. Negative Control refer to the presence of either a bound activator (+ effect on the operon; increases transcription ... provided repressor isn't blocking) vs. a bound repressor (- effect on operon; prevents transcription).

-------

Here's an analogy that might help. Consider a dimmer switch, the one where you can twist the wheel to make the light brighter and click it, to turn it on or off. Basically, the activator acts in a similar way to turning the switch (making the light more bright). This is analagous to increasing transcription. Likewise, a repressor bound is like turning off the light. Regardless of how we turn the wheel, if the light is off (repressor is bound), then nothing will happen (transcription won't proceed).

This resource might help visualize the process better: http://www.phschool.com/science/biology_place/biocoach/lacoperon/effect.html
Thanks, I think I'm getting it.
So going back to your line about the lac operon:
Again using the lac operon as our example (an inducible system). Here the inducer is allolactose. The repressor (naturally active) is bound to the operator. Once allolactose increases and then binds to the active repressor, the repressor-inducer complex becomes inactive and is no longer able to bind. This in turn, turns transcription ON.

Is having allolactose in lac operon part of its inducible system with a negative control(since we are dealing with repressor) even though the overall result turns on the transcription? And is having high levels of cyclic AMP in lac operon an example of inducible system with positive control(since we are dealing with activator)?
Thus, lac operon is an inducible system with both negative and positive control?
And trp operon is repressible system with a negative control?
So this means that inducible system can actually have either negative or positive or both control, and repressible system can also have either negative or positive, or both control?
 
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