[MUSIC] This slide represent Schleif's second major contribution. This contribution is of extreme interest for biology in general because it applies also to gene expression in yeast, drosophila, mice and man, where positive control is extremely prominent and where the regulatory region, the sites, can be very far away from the promoter. And this notion that the sites can be far away and that's what was called action at distance is something that was first described and first experimentally discussed and revealed in the arabinose system. And the second experiment was that Schleilf did an experiment with an AraC plasmid that was expressing AraC, and then he had another plasmid that was expressing AraB. These two plasmids have almost the same sequence. The AraB gene is not changed. All the regulatory sites are not changed. The only thing that's changed is the distance between 02 and I1. In this case O2 is positioned such that an AraC molecule bound here, one monomer bound here. The second monomer can bind here. The bridge is possible. You can bridge the two pieces of DNA, because the site where the protein is attaching, they are facing each other. But now the DNA, if you remember the Watson and Crick model, the DNA is a double helix. So that if you go ten base, you come back to the same position. You go ten base, you come back to the same position. So if this distance between this point, the middle of I1 and the middle of I2, is 80 base pairs, The DNA will face each other. Now imagine you add five base pairs, or you remove five base pairs, plus or minus five. This is not much in terms of distance, but this is a lot in terms of geometry. Because if your double helix is like this and ready to bind AraC, if you remove five bases, this sequence will be five bases away but it would face elsewhere. It will face 180 degree away from the AraC protein which cannot bind. You add five base, again combine, then you add another five base. You go here, but you also turn, and the protein cannot bind. So this expression, this results in a repression or no repression. And in fact you could remove repression by changing the distance between the two sides, O2 and I1. So action at a distance was a major event in our thinking about transcription. And all of this we owe to the arabinose system.