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 activate transcription through the consensus vitellogenin A2 ERE and the imperfect pS2, vitellogenin B1, and oxytocin (OT) EREs. Transient transfection experiments demonstrated that ERalpha and ERbeta 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. ERalpha and ERbeta 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. ERalpha had a higher affinity and was a more potent activator of transcription than ERbeta. Interestingly, protease sensitivity assays demonstrated that A2, pS2, B1, and OT EREs induced distinct changes in ERalpha and ERbeta conformation thereby providing different functional surfaces for interaction with regulatory proteins involved in control of estrogen-responsive genes.
Loven
M A
MA
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Ave., Urbana, IL 61801, USA.
Wood
J R
JR
Nardulli
A M
AM
D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D016466:CHO Cells; D002918:Chymotrypsin / Q000378:metabolism; D016384:Consensus Sequence / Q000235:genetics; D006224:Cricetinae; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014162:Transfection
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D004247:DNA; D002918:Chymotrypsin