Estrogen Receptors α and β Form Heterodimers on DNA

TLDR

The estrogen receptor (ER) is expressed in two forms, ERα and ERβ. Mutation analysis of the hormone‑binding domain of ERα indicates that the dimerization interface needed for heterodimer formation with ERβ is largely similar to, but not identical with, that required for homodimer formation. ERα and ERβ form heterodimers that bind DNA with a dissociation constant of ~2 nm—comparable to ERα homodimers and stronger than ERβ homodimers—and these heterodimers recruit coactivator‑1 to activate transcription, indicating functional activity in specific cell types.

Abstract

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