Endoglin expression in the endothelium is regulated by Fli-1, Erg, and Elf-1 acting on the promoter and a-8-kb enhancer

Angiogenesis is critical to the growth and regeneration of tissue but is also a key component of tumor growth and chronic inflammatory disorders. Endoglin plays a key role in anglogenesis by modulating cellular responses to transforming growth factor-beta (TGF-beta) signaling and is up-regulated in proliferating endothelial cells. To gain insights into the transcriptional hierarchies that govern endoglin expression, we used a combination of compara tive genomic, biochemical, and transgenic approaches. Both the promoter and a region 8 kb upstream of exon 1 were active in transfection assays in endothelial cells. In transgenic mice, the promoter directed low-level expression to a subset of endothelial cells. By contrast, inclusion of the -8 enhancer resulted in robust endothelial activity with additional staining in developing ear mesenchyme. Subsequent molecular analysis demonpromoter depend on conserved Ets sites, which were bound in endothelial cells in vivo by Fli-11, Erg, and Elf-1. This study therefore establishes the transcriptional framework within which endoglin functions during angiogenesis.