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

Circ Res. 2001 Feb 2;88(2):237-44. doi: 10.1161/01.res.88.2.237.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allantois / blood supply
  • Allantois / embryology
  • Allantois / metabolism
  • Animals
  • Blood Vessels / cytology
  • Blood Vessels / embryology
  • Blood Vessels / metabolism
  • Blotting, Northern
  • Cell Line
  • Chick Embryo
  • Chickens
  • Chorion / blood supply
  • Chorion / embryology
  • Chorion / metabolism
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Organ Specificity
  • Promoter Regions, Genetic / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, TIE
  • Regulatory Sequences, Nucleic Acid / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • ELF1 protein, human
  • Elf1 protein, mouse
  • Nuclear Proteins
  • Receptors, Cell Surface
  • Transcription Factors
  • ELF2 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, TIE