Ets Motifs Are Necessary for Endothelial Cell-Specific Expression of a 723-bp Tie-2 Promoter/Enhancer in Hprt Targeted Transgenic Mice

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Abstract

Objective - Tie-2 is an endothelial cell-specific receptor tyrosine kinase that is involved in the remodeling of blood vessels and angiogenesis. Our goal was to characterize Tie-2 promoter function as a means of providing insight into the mechanisms of endothelial cell-specific gene regulation. Methods and Results - When targeted to the Hprt locus of mice, a small Tie-2 promoter fragment (containing a 300-bp intronic enhancer coupled upstream to a 423-bp core promoter) (T-short) directed widespread endothelial cell expression in vivo. The T-short promoter contains 2 clusters of Ets sites, one in the first exon, the other in the intronic enhancer. In cultured endothelial cells, a combined mutation of the Ets motifs resulted in a significant reduction in promoter activity. Consistent with these results, the same Ets mutations resulted in a loss of detectable expression of the T-short promoter in all vascular beds with the notable exception of the brain. Conclusions - These results suggest that the T-short promoter contains information for widespread expression in the vascular tree, Ets sites are necessary for in vivo promoter activity, and the shorter Tie-2 fragment may be useful as a tool to direct heterologous gene expression within the intact endothelium.

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Minami, T., Kuivenhoven, J. A., Evans, V., Kodama, T., Rosenberg, R. D., & Aird, W. C. (2003). Ets Motifs Are Necessary for Endothelial Cell-Specific Expression of a 723-bp Tie-2 Promoter/Enhancer in Hprt Targeted Transgenic Mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(11), 2041–2047. https://doi.org/10.1161/01.ATV.0000089326.63053.9A

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