Vascular Biology |
From the Cardiology Division (J.G., C.V., A.D., P.O.) and New England Baptist Bone and Joint Institute (J.G., C.V., A.D., T.A.L., P.O.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass, and the Department of Molecular Cell and Developmental Biology (S.T., M.L.I.-A.), University of California at Los Angeles.
Correspondence to Peter Oettgen, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115. E-mail joettgen@ caregroup.harvard.edu
Objective The purpose of this study was to evaluate the role of the Ets factor NERF in the regulation of the Tie1 and Tie2 genes during chicken blood vessel development.
Methods and Results We have isolated the full-length cDNA for the chicken homologue of the human Ets factor NERF2 (cNERF2). Northern blot analysis and in situ hybridization demonstrate that cNERF2 is enriched in the developing blood vessels of the chicken chorioallantoic membrane. Interestingly, cNERF2 functions as a competitive inhibitor of a highly related Ets factor cELF-1, which we have previously shown to be enriched in chicken blood vessel development. Although in vitrotranslated cELF-1 and cNERF2 can bind equally well to conserved Ets binding sites in the promoters of the Tie1 and Tie2 genes, cELF-1 preferentially binds to the Ets sites in these promoters during early stages of chicken blood vessel development, suggesting that cNERF may bind during later stages of blood vessel development and vascular remodeling.
Conclusions cNERF2 is enriched during embryonic and extraembryonic blood vessel development in the chicken and facilitates tight control of Tie1 and Tie2 gene regulation.
Key Words: angiogenesis vasculogenesis transcription vascular biology endothelium
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