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Publication : A Gata2 intronic enhancer confers its pan-endothelia-specific regulation.

First Author  Khandekar M Year  2007
Journal  Development Volume  134
Issue  9 Pages  1703-12
PubMed ID  17395646 Mgi Jnum  J:121242
Mgi Id  MGI:3709677 Doi  10.1242/dev.001297
Citation  Khandekar M, et al. (2007) A Gata2 intronic enhancer confers its pan-endothelia-specific regulation. Development 134(9):1703-12
abstractText  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.
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