Transcriptional regulation of human angiopoietin-2 by transcription factor Ets-1

• Published in: Biochemical and biophysical research communications Vol. 316; no. 1; pp. 52 - 58
• Main Authors: Hasegawa, Yasuhiro, Abe, Mayumi, Yamazaki, Tohru, Niizeki, Osamu, Shiiba, Kenichi, Sasaki, Iwao, Sato, Yasufumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2004
• Subjects: Angiopoietin-2; Angiopoietin-2 - genetics; Animals; Base Sequence; Binding Sites; Cells, Cultured; Endothelial cell; Endothelium, Vascular - metabolism; Ets-1; Humans; Molecular Sequence Data; Promoter; Promoter Regions, Genetic; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ets; Response Elements; Transcription Factors - metabolism; Transcriptional Activation; Transcriptional factor; VEGF; Promoter; Angiopoietin-2; Endothelial cell; Transcriptional factor; Ets-1; VEGF
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.02.019

Angiopoietin-2 (Ang-2) plays an important role in destabilizing vessels for angiogenesis, however its transcriptional regulation has not been determined. Here we isolated about 3.2 kb of the 5 ′ upstream of the human Ang-2 gene and further characterized the transcriptional regulation of Ang-2. We found 10 Ets binding sites (EBSs) in this region. Ets-1 and Ets-2 but not Erg-1 augmented its promoter activity. Sequential deletion of EBSs and mutation analysis revealed that EBS8 located at −416/−406 from the translation initiation site was critical for Ets-1- or Ets-2-stimulated promoter activity. VEGF induced the expression of Ets-1 and Ang-2 in human umbilical vein endothelial cells (HUVECs). Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that Ets-1 bound to EBS8 in HUVECs. Moreover, synthetic double-strand oligonucleotides containing corresponding EBS8 abrogated the induction of Ang-2 by VEGF in HUVECs. These results indicate that Ets-1 and the corresponding EBS are critical for the induction of Ang-2.