Volume 272, Number 51, Issue of December 19, 1997 pp. 32613-32622

Identification of an Endothelial Cell-specific Regulatory Region in the Murine Endothelin-1 Gene

(Received for publication, July 3, 1997)

Xin Bu and Thomas Quertermous ^§

From the Departments of  Medicine and ^§ Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232

Endothelin-1 is a 21-amino acid peptide first characterized as a potent vasoactive compound synthesized by endothelial cells. Because of its high level cell-restricted pattern of expression, we have employed this gene as a model for investigating the DNA and protein elements that mediate endothelial cell-specific gene expression. In this study we have identified a complex positive regulatory region located at base pairs 364 to 320 in the murine endothelin-1 gene. This region consists of three functionally dependent elements, ETE-C, ETE-D, and ETE-E, which are all required for full activity. When a 43-base pair fragment containing these three elements was employed in heterologous promoter experiments, this sequence was capable of increasing transcriptional activity in an endothelial cell-specific fashion. None of the elements contains a recognized consensus sequence known to bind transcriptional regulatory proteins in higher eukaryotes; however, each element does appear to mediate protein binding. The combination of all three elements promotes binding of a protein complex that is endothelial cell-specific. This is the first evidence for an endothelial cell-specific DNA regulatory element and cognate binding proteins.

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