Endoglin is a component of the transforming growth factor-beta receptor com
plex whose expression is limited to a small number of cell types, including
endothelial cells (ECs), activated monocytes, tissue macrophages and eryth
roid precursors. Of particular interest is its preferential expression in t
he vasculature of many malignant tumors, especially in view of potential th
erapeutic applications. We have cloned the human endoglin promoter, analyze
d its structure and demonstrate that the isolated genomic fragment shows st
rong promoter activity in ECs (compared to other known EC-selective promote
rs), but not in epithelial cells and fibroblasts. These findings suggest th
at the endoglin promoter may prove a useful tool for the transcriptional ta
rgeting of ECs by gene therapy. We also determined the domains that are res
ponsible for both efficient transcription and the observed preferential act
ivity in ECs. The region around the major site of transcription initiation
was found to be essential for transcription in both ECs and non-ECs. In con
trast, cell type specificity does not appear to be governed by a single mec
hanism, but rather seems to be due to functionally distinct regulatory mech
anisms acting on different upstream sequences. (C) 1999 Elsevier Science B.
V. All rights reserved.