An explanation for observed estrogen receptor binding to single-stranded estrogen-responsive element DNA

Estrogen-inducible genes contain an enhancer called the estrogen response e lement (ERE), a double-stranded inverted repeat. The estrogen receptor (ER) is generally thought to bind to the double-stranded ERE. However, some rep orts provide evidence that an ER homodimer can bind a single strand of the ERE and suggest that single-stranded ERE binding is the preferred binding m ode for ER. Since these two models describe quite different mechanisms of r eceptor action, we have attempted to reconcile the observations. Analyzing DNA structure by nuclease sensitivity, we found that two identical molecule s of a single strand of DNA containing the ERE sequence can partially annea l in an antiparallel manner. Bimolecular annealing produces double-stranded inverted repeats, with adjacent unannealed tails. The amount of annealing correlates exactly with the ability of ER to bind bimolecular EREs. Either strand of an ERE could anneal to itself in a way that would bind ER. We con clude that ER binds only the annealed double-stranded ERE both in vitro and in vivo.