Lesson 7 – Video 3b
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.
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
3185 these enzymes like methylate the C bases when they occur in a CG island. Sometimes
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
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
3192 had a protein repressing this gene, now you've got covalent additions to the DNAitself
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
[00:01:47.01] OK, so here we see the structure of cytosine.And here 3196 is a methyl group
3197 put on the five position. And we call this "five methyl C" (5mC). There are a few other
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
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
3204 replication. So each cell inherits one of the original strands.And this is called
3205 meaning half methylated. And this is a signal to the cell that we should methylate this
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
3209 is highlighting the fact that if C and G is not methylated originally, it will not be
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
3213 DNAis split or replicated that the down protein will sort stochastically, ensuring that
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
3216 promoter is inherited to daughter cells.
3217 [00:04:02.06] Methylation of DNAand protein being bound to DNAbeing inherited,
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
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
3223 molecule which has a bit of a stem loop structure here.And here you can see the
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
3226 ribosomal binding site. And this is going to turn this mRNAoff so it's not making
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
3229 to make the mRNAahead of time, and just sort of occupy and hold it until you need that
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
The increased temperature would melt this stem structure, 3233 and now, exposing the
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
3236 important interactions between the DNAbinding protein and the specific DNAbinding 3237 sequence. Important binding sites for proteins are conserved more than surrounding
3238 Things that are important for function tend to get conserved. Things that are less
3239 not important, can drift evolutionarily . Mutations or base pair changes there will not
3241 [00:06:30.49] But especially in the case when you have a lock and key type scenario,
3242 sequences ha