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

doi:10.1016/j.bbrc.2004.02.019

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

New Industry Creation Hatchery Center (NICHe)

Tohoku University

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	52-58
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	316
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2004.02.019
Publication status	Published - 2004 Mar 26

Keywords

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

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10.1016/j.bbrc.2004.02.019

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title = "Transcriptional regulation of human angiopoietin-2 by transcription factor Ets-1",

abstract = "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.",

keywords = "Angiopoietin-2, Endothelial cell, Ets-1, Promoter, Transcriptional factor, VEGF",

author = "Yasuhiro Hasegawa and Mayumi Abe and Tohru Yamazaki and Osamu Niizeki and Kenichi Shiiba and Iwao Sasaki and Yasufumi Sato",

note = "Funding Information: This work was supported by the Japan Society of the Promotion of Science Research for the Future (Grant No. 99L01304).",

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AU - Hasegawa, Yasuhiro

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AU - Yamazaki, Tohru

AU - Niizeki, Osamu

AU - Shiiba, Kenichi

AU - Sasaki, Iwao

AU - Sato, Yasufumi

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N2 - 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.

AB - 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.

KW - Angiopoietin-2

KW - Endothelial cell

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KW - Promoter

KW - Transcriptional factor

KW - VEGF

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

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