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(Circulation Research. 2001;88:237.)
© 2001 American Heart Association, Inc.

Molecular Medicine

ELF-1 Is a Transcriptional Regulator of the Tie2 Gene During Vascular Development

Antoinise Dube, Shelley Thai, John Gaspar, Susan Rudders, Towia A. Libermann, Luisa Iruela-Arispe, Peter Oettgen

From the Cardiology Division (A.D., J.G., S.R., P.O.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; New England Baptist Bone and Joint Institute (A.D., J.G., S.R., T.A.L., P.O.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; and Department of Molecular Cell and Developmental Biology (S.T., L.I.-A.), University of California at Los Angeles, Los Angeles, Calif.

Correspondence to Peter Oettgen, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115. E-mail joettgen{at}caregroup.harvard.edu

Abstract—Vascular development requires the tightly coordinated expression of several growth factors and their receptors. Among these are the Tie1 and Tie2 receptors, which are almost exclusively endothelial cell–specific. The critical transcriptional regulators of vascular-specific gene expression remain largely unknown. The Ets factors are a family of evolutionarily conserved transcription factors that regulate genes involved in cellular growth and differentiation. We have recently shown that the Ets factor NERF is a strong transactivator of the Tie1 and Tie2 genes. To extend these studies, we have begun to identify the Ets factors that are expressed in developing blood vessels of the chicken chorioallantoic membrane (CAM), a highly vascular embryonic network. RNA was extracted from microdissected CAM blood vessels, and reverse transcriptase–polymerase chain reaction was performed using oligonucleotides encoding conserved amino acids within the Ets domain. One of the polymerase chain reaction fragments was subcloned and identified as the chicken homologue of the Ets factor ELF-1, cELF-1. ELF-1 is most closely related to the Ets factor NERF. In situ hybridization and immunohistochemistry demonstrate that cELF-1 is enriched in developing chicken blood vessels. cELF-1 is also a strong transactivator of the Tie1 and Tie2 genes and can bind to conserved Ets sites within the promoters of these genes. A complex of similar size forms when gel shifts are performed with cellular extracts derived from the CAM blood vessels, which is recognized by an antibody against cELF-1. In summary, ELF-1 belongs to a subset of Ets factors that regulate vascular-specific gene expression during blood vessel development.

Key Words: vascular development • angiogenesis • Tie2 gene • gene expression

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