Erratum: A few errors have been pointed out since the upload of this video. 5:19 u and d should be swapped. BREd is closer to the TSS i.e. downstream of the TATA box. 8:55 TFIID is the biggest GTF (technically). TFIIH is a close second.
Why didn't I come across this video earlier? You explain it so well and i immediately understood the concept. This channel is really underrated. Thank you so much.
Ok we have to figure out how to get you more subscribers. Your content is concise and well detailed throughout. Anyone on a undergraduate or even graduate level will benefit from these videos. People need to watch this.
@@theCrux For real, 1-2 years from now I'll become an undergraduate... Currently self-studying your translation videos, the depth is really satisfying and yet your explanation and illustrations are clear to understand! In the past, I've tried looking through academic books in my library and hardly understand anything xD. I'll look through your transcription videos after finishing both prokaryotic and eukaryotic sections
bru, where was this before my exam ! This was amazing, I love your channel so much, please never stop making videos. Also would it be possible for you inform which papers/books you used ? thank you so much :)
Hello! Glad to heat that the video is useful. I haven't kept track of my resources for the old videos, but the resources for new ones are on my Patreon. Typically, I use a lot of reviews and initial/landmark papers published in the respective video topic.
Thanks for the highly informative video. But i just have a minor clarification. According to the depiction, B reader subunit of TFII B complex is on the upstream and the region to the left of TATA box is referred as downstream. Is it interchanged ?
Thanks for asking this question. Excellent catch! Typically, you would have left side as upstream and right side as downstream (if we only look at 5' > 3' strand). In this case, the semantic argument for inverting the orientation is a bit subtle; TFIIB orients according to 3' -> 5' strand, therefore, the upstream and downstream is inverted (only for TFIIB) - I should have clarified this in the video. For simplicity, you could actually interchange and it should still be fine as long as you keep in mind that the B reader unit faces to the right of the TATA box. I hope this resolves your doubt.
Quick question: Is it known what happens to the pol II complex if the TBP were to disscociate from the TATA box during initiation/clearance? Would the pol II complex become unstable and dissociate as well? Thanks.
I am unsure of the literature that exists to answer this question, but theoretically speaking: Pol II is not recruited until TFIIF is ready to bind to the TBP. TBP (by itself or in form of TFIID) binds to other accessory factors before TFIIF has a chance, so I would assume that the kinetics would have to favor stability of TBP onto promoter to have the pol II recruited. If then promoter was weak and the TBP was not stable then it would be possible for pol II to get recruited easily. I believe (although I haven't checked the literature as much on this) that TBP > Pol II must depend on the dissociation rates/affinities of TFIIB/A + accessory factors. If the complex of TBP/TFIIA/B etc. is assembled then pol II can be recruited which then brings another set of GTFs - at this point we could argue that TBP is not going to dissociate because it gets buried in the complex. I don't know if pol II can be disassembled if you pull out TBP from the pre-initiation complex. Assuming that TBP is buried in the core of the complex (you may have to check some crystal structures to verify this) then to pull out TBP you must disassemble pol II complex first. TL;DR - I don't know enough in detail to give you a direct answer. All I can do is speculate based on the variables I know that could impact the pol II stability :)
@@theCruxThat makes sense. My thinking was that once the pol II starts synthesizing mRNA (in the abortive transcription phase) it moves, or at least tries to move, away from the TBP/TFIIB/TFIIA complex, which weakens its bond to pol II. This is something I might be able to simulate numerically and see if such dissociation leads to any observable effects, which could then be tested. Thank you for taking the time to answer my questions.
@@dXoverdteqprogress Yep, post initiation (at the least being abortive) it has to let go of the GTF complexes - otherwise it can't move past the promoter.
Is there a difference between enhancers and activators? Also, the activators are supposed to increase transcription rate. At what stage in your picture does that happen?
Thank you for the question :) Typically, when we talk about activators we usually are talking about proteins. When we call something enhancers, we are referring to the underlying DNA sequence. Activators work similar to transcription factors, in that they recruit polymerase at a defined spot. Both activators and enhancers increase transcription rate. You could also say that activators bind enhancer sequences to increase transcription. There are many caveats to everything but this is a fine generalization of enhancers and activators. In this picture, the enhancers and activators are regulatory units, and they either come during initiation (at the GTF assembly stage), before inititation (i.e. start a GTF assembly), or post initiation (i.e. to increase the transcription rate). I haven't made a video of transcriptional control and regulation yet, but at some point I will get one out. I touch a bit on these sort of factors (activators especially) and what/how they do their job in this introductory video: ua-cam.com/video/KygzEjYfUts/v-deo.html
@@theCrux Thank you for such a detailed answer. I plan to watch all your videos - they are simply fantastic! The reason for asking about activators is that I'm a physicist working in systems biology and currently I am constructing a detailed stochastic model of transcription so I can compare it to other (simpler) models. I also run a UA-cam science channel. Cheers.
@theCrux is the downstream and upstream part of the B reader element mixed up in your drawing? I am confused, I thought the BREd element is closer to the transctiption start
Yep, they did get mixed up. BREd is closer to the TSS. This BRE u/d issue has been pointed out by others as well. *Time to add an erratum for this video*
Question the little green d and u at the TFIIB part did not represent BREu&BREd right? if it's so, can I assume that the B-reader will face the direction [TATA---->BREd] but not [TATA---->BREu] ?
Ah, nice catch with d and u - they should switch places for simplicity. They represent BREd and BREu. Typically, you would have left side as upstream and right side as downstream (if we only look at 5' > 3' strand). In this case, the semantic argument for inverting the orientation is a bit subtle; TFIIB orients according to 3' -> 5' strand, therefore, the upstream and downstream is inverted (only for TFIIB) - I should have clarified this in the video. For simplicity, you could actually interchange and it should still be fine as long as you keep in mind that the B reader unit faces to the right of the TATA box. I hope this resolves your doubt.
@@theCrux thank you for your reply! it does answer my question but also leads me to have another. no matter which strand we according to, we should still recognize BREu and BREd at the same position since they are different elements, right? is it correct if I said, "BREu is in the downstream, and BREd is in the upstream of the TATA box according to 3'->5' strand "?
Thank you for this amazing explanation, however, I have a slight concern here. You mentioned TF2H is the biggest GTF, but I have read that TF2D is supposed to be the biggest GTF owing to the fact that it has TAF's which themselves contain at least 14 subunits. I might be wrong, so just raising this point here.
Ah! Thanks for picking that up. Yes, TFIID is the biggest of all (comprehensively). I usually think of GTFs as autonomous - and TFIID (which contains TBP) is not super autonomous, meaning that TBP can function without physical association of other TFIID members. TFIIH on the other hand is completely autonomous and thats why I think I said TFIIH is the biggest but that is a minority opinion ;) I will pin your comment so that others can benefit from the correction :)
@@theCrux Thank you so much, it justifies the entire argument! Also, I would like to request you to make videos on Translation, it would be super helpful! Thanks again :)
Amazing video! but i have a question about PAF1. As it is the major factor to determine the Pol to the elongation phase, which stage should it be involved according to your pictures?
I would say it is part of the transitory (initiation to elongation) as well as elongation phase. You can check out PAF complex in the elongation video as well: ua-cam.com/video/g-_nvnN32J8/v-deo.html
Isn't it too much for the students? Our prof won't explain these details to us, maybe he thinks it's too deep for us. We know there are tons of things to learn in molecular biology, so generally many prof would likely skip these complicated stuff. Do people who are at the research level suppose to know all these things ? ( I am an undergraduate)
Hello! Thanks for asking this valuable question. I would argue that if you are taking some non-molecular biology class, such that transcription is only an introductory concept, then you don't need this amount of detail. However, for a molecular biology class (especially if it is your degree's main focus), I think you need a sufficient in-depth understanding of the basic concepts like transcription, translation, and DNA replication. My videos are highly condensed form of what a typical undergrad "should" know (I leave out many things when I try to make these videos, so they are by no means complete) - no one is expected that they "should" know the concepts, but if you aim to be a molecular biologist, then these concepts are pre-requisite. Also, the type of teaching performed by professors and the expectations from the undergraduates varies from university to university (and perhaps also from country to country), so my opinion is based on the type of education I received and thus my expectation from undergraduates focusing on molecular biology. If you are at research level (i.e. molecular biology Masters, PhD, etc.), your understanding of these molecular biology concepts is expected to far exceed the content presented in these videos :) In molecular biology, I think a lot of people get stuck on the names of different things (factors, proteins, etc.) where as the point is to understand what certain proteins do and why they function like that but not some other way :) I try not to name drop too many factors and proteins (sometimes it is unavoidable) but I have to talk about "names" of proteins/enzymes/factors because pedagogically speaking, one must name/define the terms first and then use them in a lecture :) I apologize for a long response but I sincerely hope it helps (and gives you some perspective) 🙂
![Lp. Сердце Вселенной #60 РОЖДЕНИЕ ЛОЛОЛОШКИ [Финал] • Майнкрафт](http://i.ytimg.com/vi/YoR0pAV9FVQ/mqdefault.jpg)
Erratum: A few errors have been pointed out since the upload of this video.
5:19 u and d should be swapped. BREd is closer to the TSS i.e. downstream of the TATA box.
8:55 TFIID is the biggest GTF (technically). TFIIH is a close second.
Why didn't I come across this video earlier? You explain it so well and i immediately understood the concept. This channel is really underrated. Thank you so much.
Why didn’t I discover this channel sooner
My professor kept repeating the same concepts for weeks and here I’m getting the whole idea in 30 minutes
I am glad you find these videos useful 🙂
Ok we have to figure out how to get you more subscribers. Your content is concise and well detailed throughout. Anyone on a undergraduate or even graduate level will benefit from these videos. People need to watch this.
Thanks! I try 🙂
@@theCrux For real, 1-2 years from now I'll become an undergraduate... Currently self-studying your translation videos, the depth is really satisfying and yet your explanation and illustrations are clear to understand! In the past, I've tried looking through academic books in my library and hardly understand anything xD. I'll look through your transcription videos after finishing both prokaryotic and eukaryotic sections
Thank you sir
Your teaching makes my concept clear
Plz sir make the next part video of transcription
Awesome, sir please make a video for molecular techniques..Your videos super clean and thanks a lot , please keep uploading videos on this subject
Amazing video!
Such an amazing channel ❤
Keep it up sir😍
bru, where was this before my exam ! This was amazing, I love your channel so much, please never stop making videos.
Also would it be possible for you inform which papers/books you used ? thank you so much :)
Hello! Glad to heat that the video is useful. I haven't kept track of my resources for the old videos, but the resources for new ones are on my Patreon. Typically, I use a lot of reviews and initial/landmark papers published in the respective video topic.
beautiful clean explanation. love it thank you
nice explanation and sir plzzzzzzzzzzzz upload dna replication in prokaryote and eukaryote .
Thank you so much!❤
Nice 💐
Man..I love your videos...can you suggest any books for this topic??...It would be great if you suggest books in your descriptions.
Pls explain post transcriptional modifications too
Thanks for the highly informative video. But i just have a minor clarification. According to the depiction, B reader subunit of TFII B complex is on the upstream and the region to the left of TATA box is referred as downstream. Is it interchanged ?
Thanks for asking this question. Excellent catch! Typically, you would have left side as upstream and right side as downstream (if we only look at 5' > 3' strand). In this case, the semantic argument for inverting the orientation is a bit subtle; TFIIB orients according to 3' -> 5' strand, therefore, the upstream and downstream is inverted (only for TFIIB) - I should have clarified this in the video. For simplicity, you could actually interchange and it should still be fine as long as you keep in mind that the B reader unit faces to the right of the TATA box. I hope this resolves your doubt.
@@theCrux Got it! Thanks a lot bro😇
Quick question: Is it known what happens to the pol II complex if the TBP were to disscociate from the TATA box during initiation/clearance? Would the pol II complex become unstable and dissociate as well? Thanks.
I am unsure of the literature that exists to answer this question, but theoretically speaking: Pol II is not recruited until TFIIF is ready to bind to the TBP. TBP (by itself or in form of TFIID) binds to other accessory factors before TFIIF has a chance, so I would assume that the kinetics would have to favor stability of TBP onto promoter to have the pol II recruited. If then promoter was weak and the TBP was not stable then it would be possible for pol II to get recruited easily. I believe (although I haven't checked the literature as much on this) that TBP > Pol II must depend on the dissociation rates/affinities of TFIIB/A + accessory factors. If the complex of TBP/TFIIA/B etc. is assembled then pol II can be recruited which then brings another set of GTFs - at this point we could argue that TBP is not going to dissociate because it gets buried in the complex. I don't know if pol II can be disassembled if you pull out TBP from the pre-initiation complex. Assuming that TBP is buried in the core of the complex (you may have to check some crystal structures to verify this) then to pull out TBP you must disassemble pol II complex first.
TL;DR - I don't know enough in detail to give you a direct answer. All I can do is speculate based on the variables I know that could impact the pol II stability :)
@@theCruxThat makes sense. My thinking was that once the pol II starts synthesizing mRNA (in the abortive transcription phase) it moves, or at least tries to move, away from the TBP/TFIIB/TFIIA complex, which weakens its bond to pol II. This is something I might be able to simulate numerically and see if such dissociation leads to any observable effects, which could then be tested. Thank you for taking the time to answer my questions.
@@dXoverdteqprogress Yep, post initiation (at the least being abortive) it has to let go of the GTF complexes - otherwise it can't move past the promoter.
What is end use on maturity?
Is there a difference between enhancers and activators? Also, the activators are supposed to increase transcription rate. At what stage in your picture does that happen?
Thank you for the question :)
Typically, when we talk about activators we usually are talking about proteins. When we call something enhancers, we are referring to the underlying DNA sequence. Activators work similar to transcription factors, in that they recruit polymerase at a defined spot. Both activators and enhancers increase transcription rate. You could also say that activators bind enhancer sequences to increase transcription. There are many caveats to everything but this is a fine generalization of enhancers and activators.
In this picture, the enhancers and activators are regulatory units, and they either come during initiation (at the GTF assembly stage), before inititation (i.e. start a GTF assembly), or post initiation (i.e. to increase the transcription rate).
I haven't made a video of transcriptional control and regulation yet, but at some point I will get one out. I touch a bit on these sort of factors (activators especially) and what/how they do their job in this introductory video: ua-cam.com/video/KygzEjYfUts/v-deo.html
@@theCrux Thank you for such a detailed answer. I plan to watch all your videos - they are simply fantastic! The reason for asking about activators is that I'm a physicist working in systems biology and currently I am constructing a detailed stochastic model of transcription so I can compare it to other (simpler) models. I also run a UA-cam science channel. Cheers.
Thanku
@theCrux is the downstream and upstream part of the B reader element mixed up in your drawing? I am confused, I thought the BREd element is closer to the transctiption start
Yep, they did get mixed up. BREd is closer to the TSS. This BRE u/d issue has been pointed out by others as well. *Time to add an erratum for this video*
Where is there an explanation for how this gene has a unique identification?
Question
the little green d and u at the TFIIB part did not represent BREu&BREd right?
if it's so, can I assume that the B-reader will face the direction [TATA---->BREd] but not [TATA---->BREu] ?
Ah, nice catch with d and u - they should switch places for simplicity. They represent BREd and BREu. Typically, you would have left side as upstream and right side as downstream (if we only look at 5' > 3' strand). In this case, the semantic argument for inverting the orientation is a bit subtle; TFIIB orients according to 3' -> 5' strand, therefore, the upstream and downstream is inverted (only for TFIIB) - I should have clarified this in the video. For simplicity, you could actually interchange and it should still be fine as long as you keep in mind that the B reader unit faces to the right of the TATA box. I hope this resolves your doubt.
@@theCrux thank you for your reply! it does answer my question but also leads me to have another.
no matter which strand we according to, we should still recognize BREu and BREd at the same position since they are different elements, right?
is it correct if I said, "BREu is in the downstream, and BREd is in the upstream of the TATA box according to 3'->5' strand "?
Yes, they are different elements. And yes if you specify the strand for u and d context, it would be correct :)
Thank you for this amazing explanation, however, I have a slight concern here. You mentioned TF2H is the biggest GTF, but I have read that TF2D is supposed to be the biggest GTF owing to the fact that it has TAF's which themselves contain at least 14 subunits. I might be wrong, so just raising this point here.
Ah! Thanks for picking that up. Yes, TFIID is the biggest of all (comprehensively). I usually think of GTFs as autonomous - and TFIID (which contains TBP) is not super autonomous, meaning that TBP can function without physical association of other TFIID members. TFIIH on the other hand is completely autonomous and thats why I think I said TFIIH is the biggest but that is a minority opinion ;) I will pin your comment so that others can benefit from the correction :)
@@theCrux Thank you so much, it justifies the entire argument!
Also, I would like to request you to make videos on Translation, it would be super helpful!
Thanks again :)
@@lucidscience9554 Yes, I do plan on making videos on translation sometime by the end of this month :)
@@theCrux waiting eagerly for them :)
Please make video on Replication
Amazing video! but i have a question about PAF1. As it is the major factor to determine the Pol to the elongation phase, which stage should it be involved according to your pictures?
I would say it is part of the transitory (initiation to elongation) as well as elongation phase. You can check out PAF complex in the elongation video as well: ua-cam.com/video/g-_nvnN32J8/v-deo.html
Isn't it too much for the students? Our prof won't explain these details to us, maybe he thinks it's too deep for us. We know there are tons of things to learn in molecular biology, so generally many prof would likely skip these complicated stuff. Do people who are at the research level suppose to know all these things ? ( I am an undergraduate)
Hello! Thanks for asking this valuable question. I would argue that if you are taking some non-molecular biology class, such that transcription is only an introductory concept, then you don't need this amount of detail. However, for a molecular biology class (especially if it is your degree's main focus), I think you need a sufficient in-depth understanding of the basic concepts like transcription, translation, and DNA replication. My videos are highly condensed form of what a typical undergrad "should" know (I leave out many things when I try to make these videos, so they are by no means complete) - no one is expected that they "should" know the concepts, but if you aim to be a molecular biologist, then these concepts are pre-requisite. Also, the type of teaching performed by professors and the expectations from the undergraduates varies from university to university (and perhaps also from country to country), so my opinion is based on the type of education I received and thus my expectation from undergraduates focusing on molecular biology. If you are at research level (i.e. molecular biology Masters, PhD, etc.), your understanding of these molecular biology concepts is expected to far exceed the content presented in these videos :)
In molecular biology, I think a lot of people get stuck on the names of different things (factors, proteins, etc.) where as the point is to understand what certain proteins do and why they function like that but not some other way :) I try not to name drop too many factors and proteins (sometimes it is unavoidable) but I have to talk about "names" of proteins/enzymes/factors because pedagogically speaking, one must name/define the terms first and then use them in a lecture :)
I apologize for a long response but I sincerely hope it helps (and gives you some perspective) 🙂