Estrogen-receptor--DNA interaction. Difference between activation by estrogen and antiestrogen.

We have compared the interaction of the cytosol estrogen receptor with calf thymus DNA after its binding to [3H]estradiol or 4-hydroxy[3H]tamoxifen, a high-affinity antiestrogen, in an attempt to find a difference in the nature of these two complexes. The activation of the receptor and its binding to DNA were simultaneously obtained during an 18-h incubation at 0 degree C. The binding of a constant concentration of estrogen receptor to increasing concentrations of adsorbed DNA was examined. Scatchard representation of the data showed that the antiestrogen--receptor complex has a twofold lower affinity for DNA than the estradiol--receptor complex, while the proportion of receptor able to bind DNA was the same whether bound to estradiol or antiestrogen. Similar results were obtained by using soluble DNA and separation of the unbound and DNA-bound receptor on sucrose gradients. These results indicate that the estrogen receptor binds in vitro to non-specific double-stranded DNA with a lower affinity when it has been activated by an antiestrogen than when activated by estradiol.