Interaction of estrogen receptors alpha and beta 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 activat e transcription through the consensus vitellogenin A2 ERE and the imperfect pS2, vitellogenin B1, and oxytocin (OT) EREs. Transient transfection exper iments demonstrated that ER alpha and ER beta induced the highest levels of transcription with the A2 ERE, intermediate levels of transcription with t he OT ERE, and low levels of transcription with the pS2 and B1 EREs. ER alp ha and ER beta had higher affinities for the A2 ERE than for any of the thr ee imperfect EREs but similar affinities for the pS2, Bl, and OT EREs in ge l mobility shift assays. ER alpha had a higher affinity and was a more pote nt activator of transcription than ER beta. Interestingly, protease sensiti vity assays demonstrated that A2, pS2 B1, and OT EREs induced distinct chan ges in ER alpha and ER beta conformation thereby providing different functi onal surfaces for interaction with regulatory proteins involved in control of estrogen-responsive genes. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.