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) alpha and beta 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 ER alpha and ER beta 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. ER alpha and ER beta had higher affinities for the A2 ERE than for any of the three imperfect EREs but similar affinities for the pS2, Bl, and OT EREs in gel mobility shift assays. ER alpha had a higher affinity and was a more potent activator of transcription than ER beta. Interestingly, protease sensitivity assays demonstrated that A2, pS2 B1, and OT EREs induced distinct changes in ER alpha and ER beta conformation thereby providing different functional surfaces for interaction with regulatory proteins involved in control of estrogen-responsive genes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.