on the mutated GRE#2 luciferase reporter in the EcR-GR cells but not with the mutated GRE #1 reporter, indicating GRE #2 is not involved in the GR-mediated repression. FOXO1a has previously been shown to regulate SEPP1 transcription in hepatic cells through a binding site at position −46 of the promoter (Speckmann et al. 2008; Walter et al. 2008). As this regulatory mechanism involved coordination of FOXO1a with the dexamethasone-responsive cofactor PGC-1α, we also evaluated SEPP1 transcription following mutation to the FOXO1a site. Neither a change in PonA-induced SEPP1 transactivation, nor repression by GR was observed in either 293-EcR or EcR-GR cells following mutation of the FOXO1a site (Figure 5B and 5C).
