Protein-protein interactions facilitate DNA binding by the glucocorticoid receptor DNA-binding domain

We have studied the interaction of the DNA-binding domain of the glucocorticoid receptor with a glucocorticoid response element from the tyrosine aminotransferase gene. This response element consists of two binding sites (half-sites) for the glucocorticoid receptor DNA-binding domain. The sequences of these two half-sites are not identical, and we have previously shown that binding occurs preferentially to one of the half-sites (Tsai, S.-Y., Carlstedt-Duke, J., Weigel, N. L., Dahlman, K., Gustafsson, J.-A., Tsai, M.-J., and O'Malley, B. W. (1988) Cell 55, 361-369). We show here that binding to the low affinity half-site is dependent on previous occupancy of the high affinity half-site. This facilitated binding is dependent on the distance between the two half-sites and their relative orientation but is not dependent on the integrity of the DNA backbone. This is consistent with a model where DNA binding is not only dependent on interactions between the protein and its DNA target sequence but is also influenced by interactions between the protein molecules bound.