Cell type specificity of the human endoglin promoter

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.