Interaction between Transcription Factor, Basal Transcription Factor 3, and the NH2-Terminal Domain of Human Estrogen Receptor α

Abstract

The estrogen receptor (ER), like other members of the nuclear receptor superfamily, possesses two separate transcriptional activation functions, AF-1 and AF-2. Although a variety of coactivators and corepressors of AF-2 have been identified, less is known of the mechanism of action of AF-1. We have used the yeast two-hybrid system to isolate a cDNA coding for a protein that binds specifically to the AF-1 region of human ERα. This cDNA codes for the transcription factor basal transcription factor 3 (BTF3). The specificity of the interaction between BTF3 and ERα has been confirmed in vivo and in vitro. Transient transfection experiments reveal that overexpression of BTF3 modulates the transcriptional response of reporter genes to ERα. BTF3 interacts with ERα that has been activated either by 17β-estradiol (ligand-dependent activation) or by epidermal growth factor (ligand-independent activation). The effects of BTF3 on the reporter genes requires the presence of ERα containing an active AF-1 function. BTF3 may be a component of the mechanism by which the AF-1 function of ERα stimulates gene transcription. (Mol Cancer Res 2007;5(11):1191–200)