Estrogen receptors alpha and beta form heterodimers on DNA.

The estrogen receptor (ER) is expressed in two forms, ERalpha and ERbeta. Here we show that ERalpha and ERbeta, expressed both in vitro and in vivo, form heterodimers which bind to DNA with an affinity (Kd of approximately 2 nM) similar to that of ERalpha and greater than that of ERbeta homodimers. Mutation analysis of the hormone binding domain of ERalpha suggests that the dimerization interface required to form heterodimers with ERbeta is very similar but not identical to that required for homodimer formation. The heterodimer, like the homodimers, are capable of binding the steroid receptor coactivator-1 when bound to DNA and stimulating transcription of a reporter gene in transfected cells. Given the relative expression of ERalpha and ERbeta in tissues and the difference in DNA binding activity between ERalpha/ERbeta heterodimers and ERbeta it seems likely that the heterodimer is functionally active in a subset of target cells.