hi and welcome to video three in this video we're going to look at the regulation of gene expression at the transcriptional level in UK carot and also look at the role of transcription Machinery in gene expression before we jump into looking at the regulation of transcription let's do a quick review of what transcription is and how it occurs so remember transcription is the process of reading our DNA and producing our messenger RNA and then you carots remember we're going to make our pre messenger RNA first this is done by RNA polymerase 2 primarily this is the polymerase type that's responsible for making our mRNA but RNA plases don't just work by themselves they require transcription factors in order to initiate transcription these transcription factors bind to the promoter region of DNA and this will always be up stream of the gene of interest that we're trying to transcribe and these polymerases not just only depend on these they require these transcription factors in order to initiate that transcription process so there are two types of transcription factors that regulate eukariotic transcription the first set are known as general or basil transcription factors and these bind to the core promoter region to allow RNA polymerase to bind so it really recruits RNA polymerase but we also have specific transcription factors and these bind to areas that are just outside of the promoter region and in some cases kind of further away Upstream from the promoter region these are going to interact with the proteins that are on the promoter with the other transcription factors and these will either enhance or repress the activity of RNA polymerase here you can see I put a YouTube link um and what this is is at the end of this video you can go back to our canvas modules and you'll see two links one of them is this one and this video helps us review transcription and the process and role of the transcription factors that are involved in this and the next one you'll see in the next slide and this is the second video you'll see on our canvas site this one's a nice one because it shows both the basil or general transcription factors that bind to the promoter region but also it shows the specific transcription factors that are going to bind to areas far Upstream of the promoter region and it shows us how the DNA is going to be kind of bent over in order for these two types of transcription factors to interact so let's look at this line over here and pretend that over here on the right we have our Gene of interest that we're trying to transcribe in into messenger RNA Upstream of that we're going to have the promoter region and within the promoter region there will be a section known as the T box that we saw in the previous chapter so this is a nice consensus sequence that contains several thyine and adenine nucleotides here is where the first transcription Factor binds which is known as tf2d transcription Factor 2D this one happens to contain an area known as the Tata binding protein so the tf2d is the first transcription factor that will bind to the Tata box in that promoter region and that's going to recruit other transcription factors and all of these once they're bound will help RNA pmer spine to that promoter and start and activate the transcription initiation complex so here's another look at that picture that I was trying to sketch um let's ignore the other stuff for now we're going to ignore all of this we're just going to focus on this right here here is our Gene of Interest Gene a here's my promoter that's Upstream to Gene a and then I have it's not really labeled but one of these transcription factors will be my tf2d that is binding to the Tata box and the T box isn't labeled but it'll be around here in the promoter region that recruits additional transcription factors as you can see which ultim Ely recruits RNA polymerase to the promoter so now we can have the initiation of transcription remember that RNA polymerase is phosphorated and then a piece of the protein will come off before you can move RNA polymerase forward for transcription in some promoters besides the to box and tf2d that bind to the core promoter sometimes there are other binding sites that other proteins and transcription factors will bind to so they're always very close to the promoter and they're not really shown in this picture but they would be let's say around here and those would be called promoter proximal elements they would be very close to the promoter transcription factors that bind to the proximal elements or promoter proximal elements are known as six acting elements so CIS uh referring to nearby and CIS acting elements are in contrast to what we're going to see in this slide so here if I have I'm going to draw this DNA but linear instead of bent over like this let's say this is Gene a then I've got my promoter over here with my T box promoter if I look far away over here somewhere far Upstream of the promoter I might have a region called an enhancer region that that within it contains these elements known as distal control elements so these are my distal control elements activators will bind to these distal control elements so proteins called activators use different color so I could have three different activators over here these would be called activators they bind to the distal control elements and they interact with other proteins known as mediator proteins such as DNA bending protein to cause this region of the DNA to bend over like you see in this picture so that the activator proteins can interact with the transcription factors that are on the promoter to overall enhance transcription by RNA polymerase okay and then I wanted to focus on the bottom part of the slide here on the right I've got DNA bending protein that I mentioned earlier that changes the shape of DNA so that the enhancer region is closer to the core promoter region and we often have mediator proteins that are going to help the activator proteins attached to the transcription factors on the left I can see there's a note here I wanted to mention that two different genes might have the same promoter so let's say I have another DNA molecule over here molecule here this is Gene B different Gene from Gene a but it might have the same exact promoter so how do I make sure that I turn on one gene without the other and vice versa what you can have is different distal control elements that are far away from the promoter so if the set of elements here is different from the set of elements over here for g a you you can regulate which Gene is on in that particular cell in the next few slides we're going to look at more specific examples of this process here's another look at the same thing and I like this picture because it shows you the linear form of the Gene and the different control sites before it bends so I can see the gene of interest is here my promoter and TT box and far Upstream I have my enhancer with its unique distal control elements I can see activator proteins are binding to the distal control elements and along with DNA bending protein I can see that now the activator is very close or much closer to the promoter site and in order to get it Bend to get it to bend properly that DNA I can see that we have some mediator proteins this big purple complex that allows that portion of the DNA to get closer to the promoter so that it can interact with the transcription factors and promote transcription by RNA polymerase number two so at the beginning of this chapter I mentioned that all of our genes are present in all of our body cells well pretty much all of our body body cells with a few exceptions like red blood cells so that means all 46 chromosomes are present and all of those genes in those chromosomes are present in pretty much most of our body cells one example we're going to look at is here we have two genes a gene for albumin which is a protein made by the liver and a gene for crystallin which is a type of protein made in the eye these genes both of these genes are found in the liver and the lens cells of the eye but they're only expressed in their specific cell type so albumin is going to be expressed in the liver cells only and crystallin will only be expressed in the eyes so how do we make sure that albumin is not expressed in the eye or crystallin is not expressed in the liver remember that's going to be controlled by those control elements in the enhancer region that are far away from the promoter so more specifically I just wanted to show you a picture here's my liver and in the liver again I have both genes but I only want to turn on this one in contrast here is my eye and crystallin the crystallin gene is expressed to produce the protein within within our lenses so I want only the crystalline Gene to be expressed here even though both genes are present in the eye it turns out that how we regulate expression of the genes is through the specific activators that are present in each type of cell so in the liver cell we only have activators for the albumin Gene so if I look at this the activators are shown here they are available in the liver cell so they bind to those distal control elements and then here's my DNA bending protein my mediator proteins and I see a a an interaction between my activating or activator proteins and my transcription factors which promotes gene expression but but in the liver cell there are no activators for the crystalling gene so nothing happens here there's no binding there's no interaction nothing binding to the promoter and the gene for crystallin will not be expressed in contrast if I look at the cells of the lens in the eye I can see that only crystallin activators are present so again both genes are found in the lens cell of the eye but if these are my activators that are available in the lens cells they don't bind to those distal control elements for the alumin gene they one of them binds here but not all three so nothing is expressed in contrast those activators happen to be available to bind to all of the distal control elements in the enhancer region for the crystalling gene so they bind the activators bind to the enhancer region and those distal control elements I have my DNA bending protein my mediator proteins and the activator proteins interact with the transcription factors to remote gene expression of the crystall and Gene so this tells me that there's a particular combination of control elements that can activate transcription but only when the correct or appropriate activator proteins are present in the cell so it's the activator proteins that determine which genes will be expressed and activator proteins are specific to cell type and that takes us to the end of our third video in our final video we're going to look at UK carotic posttranscriptional Gene regulation protein stability and then also how altered gene expression can result in cancer