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First published online 29 March 2007
doi: 10.1242/dev.001297

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

Melin Khandekar^1,*, William Brandt^1,*, Yinghui Zhou^1,, Susan Dagenais², Thomas W. Glover², Norio Suzuki³, Ritsuko Shimizu^1,3, Masayuki Yamamoto³, Kim-Chew Lim¹ and James Douglas Engel^1,

¹ Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
² Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
³ TARA Centre, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.

Author for correspondence (e-mail: engel{at}umich.edu)

Accepted 26 February 2007

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.

Key words: Gata2, Endothelium, Cardiovascular, Lymphatic, Enhancer, ETS, SCL, Mouse

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