Sox Factors Transcriptionally Regulate ROBO4 Gene Expression in Developing Vasculature in Zebrafish
| Autor: | Mark Horswill, Ramani Ramchandran, Kallal Pramanik, Rajendra K. Kothinti, Noah R. Leigh, Mathias Francois, Monica Beltrame, George A. Wilkinson, Niloofar M. Tabatabai, Marcus O. Schupp, Ganesh V. Samant, Chang Zoon Chun, Peter Koopman, Suzanna Sellars, Indranil Sinha, Indulekha Remadevi, Silvia Moleri, Keguo Li |
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| Rok vydání: | 2011 |
| Předmět: |
SOXF Transcription Factors
Transcription Genetic DNA Mutational Analysis Receptors Cell Surface Biochemistry Mice Cell Movement Gene expression Transcriptional regulation Animals Humans Gene family Promoter Regions Genetic Molecular Biology Zebrafish Transcription factor Oligonucleotide Array Sequence Analysis Sprouting angiogenesis Regulation of gene expression Neovascularization Pathologic biology Endothelial Cells Gene Expression Regulation Developmental Cell Biology Zebrafish Proteins biology.organism_classification Molecular biology Mutation embryonic structures Developmental Biology |
| Zdroj: | Journal of Biological Chemistry. 286:30740-30747 |
| ISSN: | 0021-9258 |
| Popis: | Despite their importance as members of the Roundabout (Robo) family in the control of axonal and vascular patterning, the transcriptional regulation of these genes is poorly understood. In this study, we show that members of the Sry-related high mobility box (Sox) transcription factor family as being transcriptional regulators of roundabout4 (robo4), a Robo gene family member that participates in sprouting angiogenesis in vivo, in zebrafish. Double whole mount in situ hybridization analysis in zebrafish embryos revealed co-localization of the vascular relevant Sox factors sox7 or sox18 mRNA with robo4 transcripts in developing intersomitic vessels. A 3-kb human ROBO4 promoter element was able to drive reporter expression in zebrafish to recapitulate the endogenous temporal intersomitic vessel expression pattern of robo4. EMSA analysis confirmed binding of Sox18 to a canonical Sox binding site (from -1170 bp to -1176 bp) in the ROBO4 promoter (3 kb), and mutation analysis indicated that this site was partially responsible for ROBO4 promoter activity in ECs. A combination of gain- and loss-of-function analysis identified Sox7 and Sox18 co-regulation of robo4 but not fli1a transcripts in zebrafish. Finally, Sox-mediated robo4 transcriptional regulation is conserved across evolution. These studies imply Sox-mediated transcriptional regulation of Robo4 in the developing embryonic vasculature. |
| Databáze: | OpenAIRE |
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