Marcu Lecture 2

Marcu Lecture 2 - Lecture 2 - Slide 20-24 - How enhancers...

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Lecture 2 - Slide 20-24 - How enhancers are disnticntly unique from promoters o Enhancers are way upstream either in 5’ or 3’ o Could be found in the intron o Enhancers can function evn if the enchancer is not on the same chromosome on the gene that it is targeting o Chromosomal interactions are occurring o Truly a trans effect, it doesn’t even have to be on the same chromosome o When enhancers are driving promoters, they act like a molecular funnel, o You have a response which activates the transcription of a gene, if an enhancer is involved it acts like a magnet or a funnel for transcription activators o The transcriptional activators congregate around the enchancer o Then the enhancer communicates with the promoter o What the enhancer is doing is creating an extremely localized and transient concentration of transcriptional activators exactly when you need them and where you need them o You have this situation where what targets them is exactly how do these factors know where to go in the DNA? They have to scan the chromosomes for their binding sites, that would take a long time, so it cant just be a scanning mechanism It has to be something whereby how the factors are funneled and concentrated at the right place and right time very quickly in seconds If the activation mechanism involves something that it is independent of new protein synthesis, a fast mechanism, like a signal coming from the outside of the cell Transcription factor may even be in the cytoplasm where it is actively translocated to the nucleus very quickly or efficiently Enhancers somehow communicates with the promoters to literally attract these guys and funneling them exactly to where it needs to be
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The nuceleus is the opening in the funnel, and exactly where its going to the promoter is the little drips that come out of the final - To give a better idea of how they concentrate things… - Enhancers are similar to promoters in one major respect o They bind the exact same class of transcriptional activator proteins; the proteins hat bind to the enhancers than the class of activators that bind promoters o Sometimes, something thtat binds to the promoter of a gene, the same factor may bind to its enhancer if it has an enhancer - The difference is that the binding sites of the enhancers are highly concentrated and much more frequent with very little space of DNA between the binding sites, and so what you end up with is many transcriptional activators combined to an enhancer - Enhancers can range in size but the smallest is about 200 bp to a kilobase long - In this 200 bp, you might see as many as 12 different activators binding to 200 bp - But if you look at a 200 bp promoters, the number of activators binding at most are 6 or less than 6 - You have a two- to three fold increase over the same span of basepairs of what binding to an enhancer o Truly concentrated - Somehow molecular funneling it to the promoter - Slide 24 o Between the 20 and 260…240 bp upstream of the start sight you can have 9
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Marcu Lecture 2 - Lecture 2 - Slide 20-24 - How enhancers...

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