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Jacob-Monod: The Lac operon

Created by Tracy Kim Kovach.
Video transcript
Voiceover: So the Jacob-Monod model for gene expression describes the very first genetic regulatory mechanism to be understood clearly. When it was first described by French biologist Francois Jacob and Jacques Monad, who originated the idea that the control of enzyme levels in cells occurs through the regulation of transcription. And they, along with another scientist, shared the 1965 Nobel Prize in Medicine for their work on what is called the Lac Operon. Now a little bit of background first: An operon is a unit of genomic DNA containing a cluster of genes that are under control of a single regulatory signal, otherwise known as a promoter. And these genes are co-transcribed into a single mRNA strand and either translated together or undergo trans-splicing to create single mRNA's that are translated separately. So, basically, genes in an operon are expressed either altogether or not at all. Now, the operon that I've drawn here happens to represent the lac operon, and the lac operon is an example of an inducible set of genes which are responsible for importing and breaking down the sugar molecule lactose to use as a source of energy. So, in the event that glucose, which is the ideal source of carbon and energy for a cell, if that's not available then the cell has sort of a backup source of energy in the form of lactose. And you can see where the name lac operon comes from because it is named for the inducer molecule for the operon. And what do I mean by inducer molecule? Well, it is the presence of lactose that actually induces the transcription of the genes in this lac operon, which I'll explain in just a little bit. So, there are three coordinately regulated genes contained in the lac operon. You have the lacZ gene, which codes for an enzyme called beta-galactosidase, which is a cytoplasmic enzyme that cleaves lactoce into glucose and galactose. The next gene is the lacY gene, which codes for lactose permease, which is a cytoplasmic membrane protein that transports lactose into the cell. And then finally you have the lacA gene, which codes for thiogalactoside transacetylase. Now only the lacZ and the lacY gene are actually needed for lactose catabolism. LacA is not as important in terms of understanding how the lac operon works. Now besides these three structural genes, lacZ, Y, and A, there are two regulatory sequences contained in the lac operon, and they are called the promoter, which promotes the transcription structural genes if you will, and then also the operator. And there are two other regulatory sequences that lie just upstream of the lac operon that are genes that encode for a repressor protein, and then you have the associated promoter for that repressor protein. So, these are the structural genes here, and then here are the regulatory genes. Now, when glucose is readily available to the cell, the repressor protein is constitutively expressed, meaning that it is transcribed at base line and that is just the default. And this regulatory protein binds to the lac operator, and this interferes with and represses the binding of RNA polymerase which wants to bind here to the lac promoter. And this prevents and represses the transcription of these genes for lactose metabolism. Now, when glucose is not readily available to the cell, and an alternate source of energy is available in the form of lactose, then things start to change. First, lactose passively enters the cell at a pretty slow rate, and the metabolite of lactose, called allolactose, then binds to the repressor, and this alters the confirmation of this repressor protein, or it's shape, and it causes it to sort of loosen up and fall off the operator. Now, remember that the RNA polymerase is bound to the promoter immediately upstream of the genes. With the repressor now gone, RNA polymerase is free to sort of, picture it rolling down to transcribe all the three genes, leading to higher levels of the encoded proteins. So then you have lactose permease, which allows more lactose to enter the cell, and then you have more beta-galactosidase which can break down the lactose into galactose and glucose to be used for the cells basic metabolic needs. Now, what happens if both glucose and lactose are present? Which one does the cell prefer? Well, in that case, the transport of glucose actually blocks the transport of the inducer, the lac operon, the lactose, in a process that's called inducer exclusion. So, actually the transport of glucose into the cell leads to the formation of this protein intermediate that binds to the lactose permease and prevents it from bringing in any more lactose into the cell. Then you have decreased lactose, which leads to decreased repressor protein bindings, so then the repressor protein then sort of latches back onto the operator there and prevents the transcription of the rest of the lac operon genes. Now, there are two key take away points from the lac operon model. The first is to realize that it is the interaction between the inducer and the repressor molecules that mediate gene expression. And the second idea is that the cell expends energy to make enzymes only when necessary. So, there are inducible genes whose transcription is induced when a particular molecule is present.