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Human Estrogen Receptor β Binds DNA in a Manner Similar to and Dimerizes with Estrogen Receptor α*

P. Pace,Jacqueline A. Taylor,Sumathy Suntharalingam,R. C. Coombes,Simak Ali

Published 1997 in Journal of Biological Chemistry

ABSTRACT

The cloning of a novel estrogen receptor β (denoted ERβ) has recently been described (Kuiper, G. G. J. M., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J-A. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5925–5930 and Mosselman, S., Polman, J., and Dijkema, R. (1996)FEBS Lett. 392, 49–53). ERβ is highly homologous to the “classical” estrogen receptor α (here referred to as ERα), has been shown to bind estrogens with an affinity similar to that of ERα, and activates expression of reporter genes containing estrogen response elements in an estrogen-dependent manner. Here we describe functional studies comparing the DNA binding abilities of human ERα and β in gel shift assays. We show that DNA binding by ERα and β are similarly affected by elevated temperature in the absence of ligand or in the presence of 17β-estradiol and the partial estrogen agonist 4-hydroxy-tamoxifen. In the absence of ligand, DNA binding by ERα and β is rapidly lost at 37 °C, while in the presence of 17β-estradiol and 4-hydroxy-tamoxifen, the loss in DNA binding at elevated temperature is much more gradual. We show that the loss in DNA binding is not due to degradation of the receptor proteins. However, while the complete antagonist ICI 182,780 does not “protect” human ERα (hERα) from loss of DNA binding at elevated temperaturein vitro, it does appear to protect human ERβ (hERβ), suggestive of differences in the way ICI 182,780 acts on hERα and β. We further report that ERα and β can dimerize with each other, the DNA binding domain of hERα being sufficient for dimerization with hERβ. Cell and promoter-specific transcription activation by ERα has been shown to be dependent on the differential action of the N- and C-terminal transcription activation functions AF-1 and AF-2, respectively. The existence of a second estrogen receptor gene and the dimerization of ERα and β add greater levels of complexity to transcription activation in response to estrogens.

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