Interaction between transcription factor, basal transcription factor 3, and the NH2-terminal domain of human estrogen receptor α

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 ER alpha. This cDNA codes for the transcription factor basal transcription factor 3 (BTF3). The specificity of the interaction between BTF3 and ERa has been confirmed in vivo and in vitro. Transient transfection experiments reveal that overexpression of BTF3 modulates the transcriptional response of reporter genes to ER alpha. BTF3 interacts with ER alpha that has been activated either by 17 beta-estradiol (ligand-dependent activation) or by epidermal growth factor (ligand-independent activation). The effects of BTF3 on the reporter genes requires the presence of ER alpha containing an active AF-1 function. BTF3 may be a component of the mechanism by which the AF-1 function of ER alpha stimulates gene transcription.