A Gata2 intronic enhancer confers its pan-endothelia-specific regulation

Melin Khandekar, William Brandt, Yinghui Zhou, Susan Dagenais, Thomas W. Glover, Norio Suzuki, Ritsuko Shimizu, Masayuki Yamamoto, Kim Chew Lim, James Douglas Engel

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

GATA-2, a transcription factor that has been shown to play important roles in multiple organ systems during embryogenesis, has been ascribed the property of regulating the expression of numerous endothelium-specific genes. However, the transcriptional regulatory hierarchy governing Gata2 activation in endothelial cells has not been fully explored. Here, we document GATA-2 endothelial expression during embryogenesis by following GFP expression in Gata2-GFP knock-in embryos. Using founder transgenic analyses, we identified a Gata2 endothelium enhancer in the fourth intron and found that Gata2 regulation by this enhancer is restricted to the endocardial, lymphatic and vascular endothelium. Whereas disruption of three ETS-binding motifs within the enhancer diminished its activity, the ablation of its single E box extinguished endothelial enhancer-directed expression in transgenic mice. Development of the endothelium is known to require SCL (TAL1), and an SCL-E12 (SCL-Tcfe2a) heterodimer can bind the crucial E box in the enhancer in vitro. Thus, GATA-2 is expressed early in lymphatic, cardiac and blood vascular endothelial cells, and the pan-endothelium-specific expression of Gata2 is controlled by a discrete intronic enhancer.

Original languageEnglish
Pages (from-to)1703-1712
Number of pages10
JournalDevelopment
Volume134
Issue number9
DOIs
Publication statusPublished - 2007 May

Keywords

  • Cardiovascular
  • ETS
  • Endothelium
  • Enhancer
  • Gata2
  • Lymphatic
  • Mouse
  • SCL

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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