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Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2000, Vol. 96, No. 9, pp. 3078-3085 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Role of SCL/Tal-1, GATA, and Ets transcription factor binding sites for the regulation of Flk-1 expression during murine vascular development Andreas Kappel, Thorsten M. Schlaeger, Ingo Flamme, Stuart H. Orkin, Werner Risau, and Georg Breier From the Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany; the Center for Molecular Medicine, University of Köln, Köln, Germany; and the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA. The receptor tyrosine kinase Flk-1 is essential for embryonic blood vessel development and for tumor angiogenesis. To identify upstream transcriptional regulators of Flk-1, the gene regulatory elements that mediate endothelium-specific expression in mouse embryos were characterized. By mutational analysis, binding sites for SCL/Tal-1, GATA, and Ets transcription factors located in the Flk-1 enhancer were identified as critical elements for the endothelium-specific Flk-1 gene expression in transgenic mice. c-Ets1, a transcription factor that is coexpressed with Flk-1 during embryonic development and tumor angiogenesis, activated the Flk-1 promoter via 2 binding sites. One of these sites was required for Flk-1 promoter function in the embryonic vasculature. These results provide the first evidence that SCL/Tal-1, GATA, and Ets transcription factors act upstream of Flk-1 in a combinatorial fashion to determine embryonic blood vessel formation and are key regulators not only of the hematopoietic program, but also of vascular development. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. M. Meadows, M. C. Salanga, and P. A. Krieg Kruppel-like factor 2 cooperates with the ETS family protein ERG to activate Flk1 expression during vascular development Development, April 1, 2009; 136(7): 1115 - 1125. [Abstract] [Full Text] [PDF] L. Xu and M. Komatsu Promoter Cloning and Characterization of the Anti-vascular Proliferation Gene, R-ras: ROLE OF ETS- AND SP-BINDING MOTIFS J. Biol. Chem., January 30, 2009; 284(5): 2706 - 2718. [Abstract] [Full Text] [PDF] Y. Okada, E. Jin, V. Nikolova-Krstevski, K. Yano, J. Liu, D. 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