Interaction of estrogen receptors α and β with estrogen response elements

To understand how estrogen-responsive genes are regulated, we compared the abilities of estrogen receptors (ERs) α and β to bind to and activate transcription through the consensus vitellogenin A2 ERE and the imperfect pS2, vitellogenin B1, and oxytocin (OT) EREs. Transient transfection experiments demonstrated that ERα and ERβ induced the highest levels of transcription with the A2 ERE, intermediate levels of transcription with the OT ERE, and low levels of transcription with the pS2 and B1 EREs. ERα and ERβ had higher affinities for the A2 ERE than for any of the three imperfect EREs but similar affinities for the pS2, B1, and OT EREs in gel mobility shift assays. ERα had a higher affinity and was a more potent activator of transcription than ERβ. Interestingly, protease sensitivity assays demonstrated that A2, pS2, B1, and OT EREs induced distinct changes in ERα and ERβ conformation thereby providing different functional surfaces for interaction with regulatory proteins involved in control of estrogen-responsive genes.