Estrogen receptors alpha and beta form heterodimers on DNA

The estrogen receptor (ER) is expressed in two forms, ER alpha and ER beta. Here we show that ER alpha and ER beta, expressed both in vitro and in vivo, form heterodimers which bind to DNA with an affinity (K-d of approximately 2 nM) similar to that of ER alpha and greater than that of ER beta homodimers. Mutation analysis of the hormone binding domain of ER alpha suggests that the dimerization interface required to form heterodimers with ER beta 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 ER alpha and ER beta in tissues and the difference in DNA binding activity between ER alpha/ER beta heterodimers and ER beta it seems Likely that the heterodimer is functionally active in a subset of target cells.