Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1.

We reported previously that the sarco(endo)plasmic reticulum Ca(2+)-ATPase type 3 (SERCA3) gene is expressed in many tissues and in a subset of cells such as endothelial, epithelial, and lymphoid lineages. Here we analyzed the mechanisms involved in the regulation of transcription of the SERCA3 gene in endothelial cells. The promoter of the murine SERCA3 gene was isolated, and a single transcription initiation site located 301 bp upstream of the translation initiation site was identified. Analysis of the transcriptional activity of fragments of the SERCA3 promoter showed the existence of a minimal promoter region located between bases -97 and +153 that contains one ETS-binding site (EBS) and two Sp1 elements that are essential for basal transcription. Mutation of the EBS or of the Sp1 sites abolished the basal activity of the promoter. We identified Ets-1 and Sp1 among endothelial nuclear factors that recognize the EBS and Sp1 sites on the promoter. Furthermore, transactivation of the -97/+301 promoter fragment by Ets-1 requires the presence of both the EBS and Sp1 sites, suggesting an interaction of the transcription factors on the gene promoter. Finally, overexpression of Ets-1 induced the expression of SERCA3 in endothelial cells and in fibroblasts.