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.
Dahlman-Wright
K
K
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
Siltala-Roos
H
H
Carlstedt-Duke
J
J
Gustafsson
J A
JA
D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005796:Genes; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D014444:Tyrosine Transaminase / Q000235:genetics*
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; D004247:DNA; D014444:Tyrosine Transaminase