OBJECTIVE: Angiopoietin-2 (Ang-2) is a non-signal transducing ligand of the endothelial receptor tyrosine kinase Tie-2. Ang-2 is produced by endothelial cells and acts as an autocrine regulator mediating vascular destabilization by inhibiting Angiopoietin-1-mediated Tie-2 activation. To examine the transcriptional regulation of Ang-2, we studied the Ang-2 promoter in endothelial cells and nonendothelial cells. METHODS AND RESULTS: The human Ang-2 promoter contains a 585-bp region around the transcriptional start site (-109 to +476) that is sufficient to control endothelial cell-specific and cytokine-dependent Ang-2 expression. Strong repressor elements of Ang-2-promoter activity are located in the 5'-region of the promoter and in the first intron. The Ets family transcription factors Ets-1 and Elf-1 act as strong enhancers of endothelial cell Ang-2-promoter activity. Ets-binding sites -4 and -7 act as positive regulators, whereas Ets-binding site -3 acts as negative regulator. Demethylation experiments revealed that the Ang-2 gene (in contrast to the Tie-2 gene) is not controlled by imprinting. CONCLUSIONS: The data determine unique positive and negative regulatory mechanisms of endothelial cell Ang-2 expression and provide further evidence for the critical role of Ang-2 as a key autocrine regulator of vascular stability and responsiveness.
OBJECTIVE:Angiopoietin-2 (Ang-2) is a non-signal transducing ligand of the endothelial receptor tyrosine kinase Tie-2. Ang-2 is produced by endothelial cells and acts as an autocrine regulator mediating vascular destabilization by inhibiting Angiopoietin-1-mediated Tie-2 activation. To examine the transcriptional regulation of Ang-2, we studied the Ang-2 promoter in endothelial cells and nonendothelial cells. METHODS AND RESULTS: The humanAng-2 promoter contains a 585-bp region around the transcriptional start site (-109 to +476) that is sufficient to control endothelial cell-specific and cytokine-dependent Ang-2 expression. Strong repressor elements of Ang-2-promoter activity are located in the 5'-region of the promoter and in the first intron. The Ets family transcription factors Ets-1 and Elf-1 act as strong enhancers of endothelial cell Ang-2-promoter activity. Ets-binding sites -4 and -7 act as positive regulators, whereas Ets-binding site -3 acts as negative regulator. Demethylation experiments revealed that the Ang-2 gene (in contrast to the Tie-2 gene) is not controlled by imprinting. CONCLUSIONS: The data determine unique positive and negative regulatory mechanisms of endothelial cell Ang-2 expression and provide further evidence for the critical role of Ang-2 as a key autocrine regulator of vascular stability and responsiveness.
Authors: Sebastien P Tabruyn; Katharine Colton; Tohru Morisada; Jonas Fuxe; Stanley J Wiegand; Gavin Thurston; Anthony J Coyle; Jane Connor; Donald M McDonald Journal: Am J Pathol Date: 2010-10-15 Impact factor: 4.307
Authors: Anthony J Connor; Radosław P Nowak; Erica Lorenzon; Markus Thomas; Frank Herting; Stefan Hoert; Tom Quaiser; Eliezer Shochat; Joe Pitt-Francis; Jonathan Cooper; Philip K Maini; Helen M Byrne Journal: J R Soc Interface Date: 2015-09-06 Impact factor: 4.118
Authors: Fernando J Calero-Nieto; Andrew D Wood; Nicola K Wilson; Sarah Kinston; Josette-Renée Landry; Berthold Göttgens Journal: Nucleic Acids Res Date: 2010-06-04 Impact factor: 16.971