HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels

Mech Dev. 1997 Apr;63(1):51-60. doi: 10.1016/s0925-4773(97)00674-6.


Transcription factors of the bHLH-PAS protein family are important regulators of developmental processes such as neurogenesis and tracheal development in invertebrates. Recently a bHLH-PAS protein, named trachealess (trl) was identified as a master regulator of tracheogenesis. Hypoxia-inducible factor, HIF-1 alpha, is a vertebrate relative of trl which is likely to be involved in growth of blood vessels by the induction of vascular endothelial growth factor (VEGF) in response to hypoxia. In the present study we describe mRNA cloning and mRNA expression pattern of mouse HIF-related factor (HRF), a novel close relative of HIF-1 alpha which is expressed most prominently in brain capillary endothelial cells and other blood vessels as well as in bronchial epithelium in the embryo and the adult. In addition, smooth muscle cells of the uterus, neurons, brown adipose tissue and various epithelial tissues express HRF mRNA as well. High expression levels of HRF mRNA in embryonic choroid plexus and kidney glomeruli, places where VEGF is highly expressed, suggest a role of this factor in VEGF gene activation similar to that of HIF-1 alpha. Given the similarity between morphogenesis of the tracheal system and the vertebrate vascular system, the expression pattern of HRF in the vasculature and the bronchial tree raises the possibility that this family of transcription factors may be involved in tubulogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Brain / blood supply
  • Brain / embryology
  • Capillaries
  • Cloning, Molecular
  • DNA Primers
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • Endothelium, Vascular / embryology
  • Endothelium, Vascular / physiology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Helix-Loop-Helix Motifs
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / chemistry
  • Organ Specificity
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • RNA, Messenger / biosynthesis
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription Factors / biosynthesis*
  • Transcription Factors / chemistry
  • Transcription, Genetic*
  • Transcriptional Activation
  • Vertebrates


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • endothelial PAS domain-containing protein 1

Associated data

  • GENBANK/AF045160