Lesson 7 – Video 1
2725 [00:00:01.08] SPEAKER: Hi there. In today's series of videos, we're going to talk about
2726 specific transcription. In the previous class, we talked about general features of
2727 translation. What genes, in general, have to happen for genes to get turned on or off. But
2728 enough to be able to turn genes on or off. You have to turn on selective genes when you
2729 them, and keep others off when you need them to be off.
2730 [00:00:27.82] So this is about a higher level of control.And the very basic switch in that
2731 is a DNAbinding protein binding to a DNAspecific sequence to turn a gene on that's
2732 that locality. Call this a lock and a key. The pieces have to fit perfectly. They're made to
2733 each other.And that's how a gene can be activated.
2734 [00:00:56.12] We'll look at some of the molecular details, in terms of how proteins
2735 which I say is reading the code of the DNAin the major and minor grooves to recognize
2736 the gene that I'm supposed to turn on.And then lastly, in this video we'll talk extremely
2737 about some different classes of DNAbinding proteins or transcription factors.
2738 [00:01:22.38] And this slide sort of highlights the point. Let's start with the carrot. Here
2739 a single cell with one nucleus, with one copy of the genome, and yet all the information
2740 so that it, over time, develops from a young embryo, young plant, finally to a mature
2741 This is a timed orchestration of turning genes on and off so they produce the proper
2742 the proper time, the proper molecules. They build the proper structures, and in the end,
2743 life cycle to continue.And they have produced an adult functioning organism.
2744 [00:02:07.51] The frog and the cow examples focus in on the cloning techniques, and
2745 discuss those later in the course. But it's the same thing as how do the various
2746 are contained in the DNAbe deployed in a time dependent manner to produce the final
2747 an adult organism?
2748 [00:02:31.52] So here we see a slide again. Six levels where genes can be controlled
2749 functions modulated so that you can have, in the end, an active protein doing a job that
2750 it to do. We'll talk mostly today about this very first step, transcriptional control.
Because of its 2751 primacy, it's one of the best studied of these features.And it is, as you know, in essence,
2752 20,000 to 25,000 genes, which ones are we going to turn on at this particular time to
next steps that we need to do in order to respond to the environment 2753 or carry out the
plan that is
2754 inherent in our genome?
2755 [00:03:17.97] Once you've made the RNA, there's lots of other ways to influence this
2756 getting to the active protein, processing the RNA, transporting the RNA, binding to it,
2757 localization, making it free and available, or sequestering it from being used. There is
2758 how much protein is made for each mRNA, how actively or quickly the mRNA is
2759 folded proteins' activity is controlled. Because an inactive verses an active protein can
2760 completely different results.And by the second part of this course, we will have
discussed all of
2761 these in pretty decent detail.
2762 [00:04:10.55] OK, transcriptional control. Two basic components, a lock and key. The
2763 equivalents are a short stretch of a defined DNAsequence. This is the gatekeeper for a
2764 a gene regulatory protein that recognizes and binds to that sequence. This is the key
that's sort of
2765 opening the lock or turning the gene on.
2766 [00:04:42.51] So how will the proteins read the sequence that is present? We know--
this is a
2767 picture from a previous slide-- how DNArecognizes itself.Aand T participate in
2768 bonding.And T recognizes anAby two hydrogen bonds.And C recognizes G by three
2769 bonds. But the protein is not able to recognize these bases based on this base pairing. It
is in the
2770 center here of the DNAdouble helix, and they are occupied with each other. That is not
2772 [00:05:21.12] What is available to the proteins is the ends that are exposed in the major
2773 minor grooves.And although it's poorly drawn, this is what-- the protein C is looking at
2774 this is what's in the major groove. Same here. Down here. This side is, in the way it's
2775 this book, which is this is a poor representation of the actual geometry, is what's seen in
2776 minor groove.
2777 [00:05:56.14] So let's look here. Let's look at a particular slice, right here in the end on
of a base
2778 pair. You could see hydrogens; carbons, the darker blue; nitrogens, the lighter blue;
carbon, 2779 hydrogen, nitrogen, and oxygen.And this pattern, which we will schematize on the next
2780 how DNAbinding protein recognizes whether it is a G, a C, anA, or a T, at that
2781 has the ability to query several base pairs at a particular time. You'll see, because of the
2782 of the double helix, because it is twisting, that it's going to be hard for a single protein,
2783 instance, to recognize 20 consecutive bases.
2784 [00:06:58.64] Because of the approach, it might be able to recognize quite a few. But it
2785 recognize five here, down here, and five here, just because that is the face of the DNA
2786 exposed to the protein. And here we make that clearer. This is drawn to better
2787 it's color coded in a very convenient way. So let's imagine the protein is approaching
2788 base pair from the major groove. It'll see a hydrogen, nitrogen, oxygen, a hydrogen, a
2789 and a hydrogen.
2790 [00:07:39.09] Also note that, if we go left to right, a GC base pair will look different to
it than a
2791 CG base pair. So the proteins distinguish between these two binding situations. If we
the GC to theAT, we can see, for instance, that the G will see if it's 2792 looking at a G, it's
2793 see an oxygen here where it's seeing a hydrogen in sort of the complementary position.