Regulation of the Estrogen Receptor α Minimal Promoter by Sp1, USF-1 and ERα

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Abstract
The exact molecular mechanisms regulating estrogen receptor α (ERα) expression in breast tumors are unclear, but studies suggest that they are partly at the level of transcription. We have focused on the transcription factors that regulate the ERα minimal promoter, which we have previously shown to reside within the first 245 bp of the 5′-flanking region of the gene. Within this region are several elements essential for full ERα promoter transcriptional activity, including a GC box and an imperfect E box. In earlier studies we demonstrated an essential function for the Sp1 family of transcription factors in the regulation of ERα expression. We have now identified both USF-1 and ERα itself as components of a multi-protein complex of transcription factors that interacts at the ERα minimal promoter and is essential for its full transcriptional activity. Electrophoretic mobility shift assays demonstrated that Sp1 and USF-1, but not ERα, bind directly to the ERα minimal promoter. We showed by GST pull-down assays that ERα is able to interact in vitro with USF-1, suggesting, in addition to a possible interaction between ERα and Sp1, a mechanism whereby ERα is able to interact with the protein complex. Combined exogenous expression of the components of the complex in MCF-7 breast cancer cells resulted in a synergistic effect on transactivation of the ERα minimal promoter, suggesting that the importance of the protein complex is in the interactions among the components. Based upon these findings, we propose a possible model for transcription from the ERα minimal promoter.