Molecular model of the interaction between the glucocorticoid receptor and the regulatory elements of inducible genes.

Binding sites for the glucocorticoid receptor in an ecdysone-inducible gene from Drosophila melanogaster and in the chicken vitellogenin gene are described. A comparison with other binding sites for the glucocorticoid receptor, which have been analyzed by methylation protection experiments, shows they can be classified into three groups. The first group exhibits two blocks of contact points in two subsequent turns of the DNA helix, and includes only functional regulatory elements. The second group shows an identical contact with the hexanucleotide 5'-TGTYCT-3', but only half the contact points in the other turn of the helix, whereas the third group of sites exhibits only the contact points within the conserved hexanucleotide. An analysis of the hydrogen-bonding potential of the DNA base pairs along the major groove of 10 binding sites shows a very well-conserved pattern and a twofold rotational symmetry, suggesting that the array of hydrogen bonds may be a relevant aspect of sequence recognition by hormone receptors. A representation of the binding sites and contact points by computer graphics suggests the interaction of a receptor dimer, in a head-to-head arrangement, with two subsequent turns of the B-DNA helix within the glucocorticoid regulatory elements.