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 language | English |
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Pages (from-to) | 1703-1712 |
Number of pages | 10 |
Journal | Development |
Volume | 134 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2007 May |
Externally published | Yes |
Keywords
- Cardiovascular
- ETS
- Endothelium
- Enhancer
- Gata2
- Lymphatic
- Mouse
- SCL
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology