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

Yasuhiro Hasegawa, Mayumi Abe, Tohru Yamazaki, Osamu Niizeki, Kenichi Shiiba, Iwao Sasaki, Yasufumi Sato

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42 Citations (Scopus)


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 3.2kb 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.

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2004 Mar 26


  • Angiopoietin-2
  • Endothelial cell
  • Ets-1
  • Promoter
  • Transcriptional factor
  • VEGF


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