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A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo
- Source :
- Blood. 112:2336-2339
- Publication Year :
- 2008
- Publisher :
- American Society of Hematology, 2008.
-
Abstract
- 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.
- Subjects :
- Transgene
Transplantation, Heterologous
Immunology
Mutant
lac operon
Mice, Transgenic
Receptors, Cell Surface
Embryoid body
Biology
Hemostasis, Thrombosis, and Vascular Biology
Biochemistry
Mice
In vivo
Animals
Humans
Tissue Distribution
Endothelium
Promoter Regions, Genetic
Gene
Binding Sites
Promoter
Neoplasms, Experimental
Cell Biology
Hematology
Embryo, Mammalian
GA-Binding Protein Transcription Factor
Molecular biology
Transplantation
Mutation
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 112
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....bb12ea793a57d385899ed9c83acb7a6d