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Lecture 7

Cell Biology - Lecture 7 - Video 3.2 - Notes

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CAS BI 203
Martin Steffen

Lesson 7 – Video 3b [00:00:00.00] 3180 [00:00:00.77] DR. MARTIN STEFFEN: Hi. I'd like to resume the conversation on gene 3181 regulation to talk about epigenetics. In particular, we'll start with DNAmethylation. "Epi" means 3182 around, so it's not truly genetics. It's not changing the base sequence C,A, G, and T. 3183 [00:00:18.56] But what can happen is you can methylate, you can add a methyl group to 3184 cytosines.And we'll see methyl C on the next slide. But for now, we'll just note that in particular, 3185 these enzymes like methylate the C bases when they occur in a CG island. Sometimes you say 3186 CpG island, which is inferring that it's a 5' to 3' direction, so when C precedes G. 3187 [00:00:49.04] And you have some CG clusters in promoter regions. So when these get 3188 methylated, different types of gene regulation will occur. In particular, many genes will get 3189 turned off if their promoters are methylated. 3190 [00:01:08.35] But I'll say as an aside, methylation can also turn on some other promoters. But the 3191 general case is that it's going to turn things off.And now you've, whereas before you might have 3192 had a protein repressing this gene, now you've got covalent additions to the DNAitself that's 3193 going to make this gene turned off.And now this repressor protein could leave if it needed to, or 3194 did by random events. The gene would still be turned off with these methyl marks here in the 3195 promoter. 88 [00:01:47.01] OK, so here we see the structure of cytosine.And here 3196 is a methyl group that gets 3197 put on the five position. And we call this "five methyl C" (5mC). There are a few other locations 3198 of methylation-- for instance,Acan also get methylated-- but the most important of these is five 3199 methyl cytosine. 3200 [00:02:08.40] So we see this is referred to as epigenetics because this methylation status can get 3201 inherited. See the case where you have fully methylated DNA.Again, CpG islands are 3202 palindromic. Both strands are methylated. 3203 [00:02:25.91] Now we're going to get DNAreplication. You're going to have semiconservative 3204 replication. So each cell inherits one of the original strands.And this is called hemimethylated, 3205 meaning half methylated. And this is a signal to the cell that we should methylate this other 3206 cytosine base. 3207 [00:02:50.03] And so what's being inherited is the methylation status at a particular gene. So the 3208 daughter cells are going to stay methylated.And I guess I should have pointed out that this figure 3209 is highlighting the fact that if C and G is not methylated originally, it will not be methylated in 3210 the daughter cell. 3211 [00:03:14.95] Events at the protein level, we found, can be inherited also.And that is that if a 3212 gene is turned off and there are many copies of repressor proteins in a promoter region when the 3213 DNAis split or replicated that the down protein will sort stochastically, ensuring that both 3214 daughter cells get some of the protein which, aided by cooperative binding, will serve as a nidus 3215 for additional proteins to bind at the promoter. So in this case, the protein being bound at a 3216 promoter is inherited to daughter cells. 3217 [00:04:02.06] Methylation of DNAand protein being bound to DNAbeing inherited, again, 3218 that's sort of a generic term for what's referred to as epigenetics. So we've talked almost 3219 exclusively about transcriptional regulation.And I've mentioned before that you can also, once 3220 an mRNA is made, control how much protein is made of from that mRNA. 3221 [00:04:29.64] And actually, it's highly frequent, as we'll see in the third portion of course. I just 3222 want to give a flavor of it right now, because it's not as well-characterized. But here's an mRNA 3223 molecule which has a bit of a stem loop structure here.And here you can see the ribosomal 3224 binding site, which is where the ribosome has to bind in order to make this protein. 3225 [00:04:56.90] If a translation repressor protein binds this mRNA, that's going to occupy the 3226 ribosomal binding site. And this is going to turn this mRNAoff so it's not making protein. Why 3227 might you want to do that, you ask? 3228 [00:05:10.85] Well, if you want to enable a quick response to a certain stimulus, you might want 3229 to make the mRNAahead of time, and just sort of occupy and hold it until you need that protein. 3230 Then can make the protein much more quickly when you need it. 3231 [00:05:29.55] Another way genes can be regulated is if the ribosomal binding site is here in the 3232 stem loop structure.And these might be some genes that get turned on in terms of heat response. 89 The increased temperature would melt this stem structure, 3233 and now, exposing the ribosomal 3234 binding site, allowing this protein to get made.And there are many others as well. 3235 [00:05:57.69] I'd like to conclude the series of videos to talk about how people study these 3236 important interactions between the DNAbinding protein and the specific DNAbinding 3237 sequence. Important binding sites for proteins are conserved more than surrounding sequence. 3238 Things that are important for function tend to get conserved. Things that are less important, or 3239 not important, can drift evolutionarily . Mutations or base pair changes there will not really affect 3240 function. 3241 [00:06:30.49] But especially in the case when you have a lock and key type scenario, those 3242 sequences ha
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