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Publication : A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo.

First Author  Okada Y Year  2008
Journal  Blood Volume  112
Issue  6 Pages  2336-9
PubMed ID  18519813 Mgi Jnum  J:138735
Mgi Id  MGI:3806211 Doi  10.1182/blood-2008-01-135079
Citation  Okada Y, et al. (2008) A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo. Blood 112(6):2336-9
abstractText  We recently demonstrated that the 3-kb 5'-flanking region of the human ROBO4 gene directs endothelial cell-specific expression in vitro and in vivo. Moreover, a GA-binding protein (GABP)-binding motif at -119 was necessary for mediating promoter activity in vitro. The goal of the present study was to confirm the functional relevance of the -119 GABP-binding site in vivo. To that end, the Hprt locus of mice was targeted with a Robo4-LacZ transgenic cassette in which the GABP site was mutated. In other studies, the GABP mutation was introduced into the endogenous mouse Robo4 locus in which LacZ was knocked-in. Compared with their respective controls, the mutant promoters displayed a significant reduction in activity in embryoid bodies, embryos, and adult animals. Together, these data provide strong support for the role of the GABP-binding motif in mediating Robo4 expression in the intact endothelium.
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