Functional differences between the amino-terminal domains of estrogen receptors alpha and beta.
Human estrogen receptors alpha (ERalpha) and beta (ERbeta) are ligand-inducible transcription factors that are highly homologous in their central DNA-binding and carboxyl-terminal ligand-binding domains. In contrast, there is very little conservation between ERalpha and ERbeta in the amino-terminal domain. Using different human cell lines, we show that wild-type ERbeta transcriptional activity is lower or similar to that of ERalpha, depending on the cell type. Deletion of the amino-terminal domain in both ER subtypes resulted in no or a lower decrease of transcriptional activity of ERbeta compared with ERalpha, suggesting that the ERbeta amino-terminal domain contains a weaker transcriptional activation function-1. Using ERalpha and ERbeta deletion mutants, we showed that the amino-terminal transcriptional activity of ERbeta maps to amino acids 1-31. Interestingly, this domain contains a six amino-acid motif (amino acids 5-10 in human ERbeta) that is part of the ERalpha-activation function-1 region (amino acids 49-54 in human ERalpha) and highly conserved among all mammalian ERalpha amino-terminal domains. Despite this similarity between the two ER subtypes, no autonomous and ligand-independent activity of the ERbeta-amino-terminal domain was observed in yeast and mammalian cells in contrast to ERalpha. This study provides a molecular basis for the difference in transcriptional activity between ERalpha and ERbeta and establishes that ERbeta contains a structurally and functionally restricted amino-terminal transcriptional activity.
Delaunay
F
F
Department of Medical Nutrition and Center for Biotechnology, NOVUM, Karolinska Institute, Huddinge, Sweden.
Pettersson
K
K
Tujague
M
M
Gustafsson
J A
JA
D002478:Cells, Cultured; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen