Lesson 7 – Video 2b
[00:00:00.76] DR. MARTIN STEFFEN: OK, resuming 2940 our discussion about complex
2941 regulation-- now, in this slide, we're going to see how the cell controls sugar
metabolism. And in
2942 particular, we're going to look how it regulates the gene expression based on the
presence of two
2943 sugars-- glucose, which is its preferred sugar source, or lactose.
2944 [00:00:28.69] It can use lactose to grow. But it only likes to do so when no glucose is
2945 Because it's a less efficient sugar to be used. The genes we're going to turn on or off is
2946 operon. Here, we see the lac Z gene. Plus, there are about three other lac genes at this
2947 [00:00:50.86] And we have two proteins that are going to be involved-- a repressor and
2948 activator, which will bind depending on whether glucose or lactose are present. The
2949 protein binds in response to lactose. The blue protein binds and responds to a molecule
2950 cyclicAMP, which is related to the glucose concentration.
2951 [00:01:19.81] And again, the important point is you only want to turn on these lactose
2952 lactose is present but glucose is absent. When lactose is your only possible source of
2953 want to make the lactose genes so you can take advantage of the presence of lactose. If
2954 present, making these lactose genes is a waste of time and energy. You will be much
2955 just using the glucose directly. So that's why it shuts them off when glucose is present.
2956 [00:01:52.85] So I think it's best to start with this case number two. That means glucose
2957 present, and there's no lactose in the environment. Then, for sure no lactose is present,
2958 to make sure the lactose genes are not going to be made.And because there's no lactose
2959 there's this repressor protein, who's normal state is to bind the DNA. It's normally
2960 lactose genes.
2961 [00:02:24.28] Now, in the situation when lactose gets added to the environment, just
like in the
2962 trp repressor, the molecule lactose will bind to the repressor. It will cause a change in
2963 confirmation preventing it from binding to the DNA.
2964 [00:02:42.96] Now the repressor is not able to bind. So the repressor will not stop the
2965 of these genes. But you still don't want to make them. Because you'd rather use glucose.
So the 2966 point is the default setting here is to not make the genes. You don't have enough to get
2967 genes started. Because you still don't want them. Because you have glucose present.
2968 [00:03:08.98] Now, the third case is there's no glucose and there's no lactose. Well, you
2969 glucose. Because it's not there. But you still don't want to make the lactose genes. So
2971 [00:03:21.50] Since there's no lactose to bind to the repressor, it's bound to the DNA,
2972 the repressor's normal state. But now, since there's no glucose, there's increased
2973 cyclicAMP. CyclicAMP, that's that red triangle right here. I'll circle it.
2974 [00:03:39.86] It binds to the CAP protein, which changes the confirmation.And this is a
2975 to say, hey, we might need to use these genes. Because we don't have glucose. But the
think, but we don't have lactose anyway. So let's not bother. It's 2976 only in the last case
2977 there's no glucose, so you have high levels of cyclicAMP.
2978 [00:04:03.24] So the CAP protein is binding to the DNA, providing extra
2979 binding energy to help recruit the RNApolymerase to the promoter.And since there is
2980 present, lactose is bound to the repressor. The repressor has fallen off.And now, you
2981 the genes that are going to help you metabolize lactose. So in this very simple way,
2982 proteins, one an activator, one a repressor, you can respond to a variety of
2983 conditions and make the proper choices on gene synthesis.
2984 [00:04:39.90] Now, most of what we've been talking with the Trp repressor and the lac
2985 have been for bacteria. In eukaryotes, things are a little more complex, a little more
2986 The default setting for most of human genes is to do nothing.
2987 [00:05:00.06] So in general, there's extra emphasis placed on activation.And in fact,
2988 polymerase II, which is the RNApolymerase that makes messenger RNAin humans, or
2989 eukaryotes, use, generally, multiple transcription factors to begin transcription. Even
2990 just saw examples where a single protein could help recruit the polymerase, in
2991 frequently the case that many proteins help recruit RNApolymerase.
2992 [00:05:29.18] Eukaryotic cells do not have operons. Each gene is regulated individually.
2993 distances involved in regulation can be much larger. There can be certainly many tens
of 2994 thousands of bases between transcription start site and these regulators bound in, and
2995 hundreds of thousands of base pairs.
2996 [00:05:51.08] And lastly, you might recall that when we were talking about
2997 are things like euchromatin and heterochromatin.And in general, the density of histone
2998 around genes provides another level at which genes can be regulated.
2999 [00:06:09.17] So in this slide, which is pretty general, this shows a possible eukaryotic
3000 Here, we have RNApolymerase, the TATAbinding protein, the general transcription
3001 which we called TAFs, or TranscriptionAccessory Factors. They've helped recruit the
3002 polymerase to the promoter region.And it will transcribe this gene stopping.
3003 [00:06:34.36] Here is the implication. Right upstream-- again, this is at the minus 10
3004 35 spot-- this location where you have gene-specific regulatory proteins or transcription
3005 this could be a few hundred bases from the promoter. These sequences up here could be
3006 thousand.And here, we could have a protein t