Sp1 transcription factor expression is regulated by estrogen-related receptor α1

The current study examines the relationship between ERRα1 and the Sp1 transcription factor. The transfection of ERRα1 enhances Sp1-DNA complex formation as visualized by electrophoresis mobility shift assay (EMSA). In addition, luciferase activity under the control of three consensus sites for Sp1 binding is activated by ERRα1 transfection. By looking further upstream from this point we have found that ERRα1 stimulates the upregulation of Sp1 protein expression by activating its transcription. Indeed, human Sp1 promoter-dependent luciferase activity is activated by ERRα1 transfection and a DNA-protein complex is observed by EMSA using oligonucleotides encompassing the putative ERRα1 binding site on the human Sp1 promoter (−1444/−1433: 5′-AGGACATGACCT-3′). In addition, activation of Sp1 promoter-dependent luciferase activity depends on the A/B and C domains of ERRα1 as shown with truncated ERRα1 cDNAs. This report is the first to demonstrate that ERRα1 promotes Sp1 activity through upregulation of Sp1 expression at the transcriptional level.