ELF-1 is a transcriptional regulator of the Tie2 gene during vascular development

Vascular development requires the tightly coordinated expression of several growth factors and their receptors. Among these are the Tie1 and Tie2 rece ptors, which are almost exclusively endothelial cell-specific. The critical transcriptional regulators of vascular-specific gene expression remain lar gely unknown. The Ets factors are a family of evolutionarily conserved tran scription factors that regulate genes involved in cellular growth and diffe rentiation. We have recently shown that the Ets factor NERF is a strong tra nsactivator of the Tie1 and Tie2 genes. To extend these studies, we have be gun to identify the Ets factors that are expressed in developing blood vess els of the chicken chorioallantoic membrane (CAM), a highly vascular embryo nic network. RNA was extracted from microdissected CAM blood vessels, and r everse transcriptase-polymerase chain reaction was performed using oligonuc leotides encoding conserved amino acids within the Ets domain. One of the p olymerase chain reaction fragments was subcloned and identified as the chic ken homologue of the Ets factor ELF-1, cELF-1. ELF-1 is most closely relate d to the Ets factor NERF. In situ hybridization and immunohistochemistry de monstrate that cELF-1 is enriched in developing chicken blood vessels. cELF -1 is also a strong transactivator of the Tiel and Tie2 genes and can bind to conserved Ets sites within the promoters of these genes. A complex of si milar size forms when gel shifts are performed with cellular extracts deriv ed from the CAM blood vessels, which is recognized by an antibody against c ELF-1. In summary, ELF-1 belongs to a subset of Ets factors that regulate v ascular-specific gene expression during blood vessel development.