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

Transcription factors of the bHLH-PAS protein family are important reg ulators of developmental processes such as neurogenesis and tracheal d evelopment in invertebrates. Recently a bHLH-PAS protein, named trache aless (trl) was identified as a master regulator of tracheogenesis. Hy poxia-inducible factor, HIF-1 alpha, is a vertebrate relative of trl w hich is likely to be involved in growth of blood vessels by the induct ion of vascular endothelial growth factor (VEGF) in response to hypoxi a. In the present study we describe mRNA cloning and mRNA expression p attern of mouse HIF-related factor (HRF), a novel close relative of HI F-1 alpha which is expressed most prominently in brain capillary endot helial cells and other blood vessels as well as in bronchial epitheliu m 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 embryo nic choroid plexus and kidney glomeruli, places where VEGF is highly e xpressed, suggest a role of this factor in VEGF gene activation simila r to that of HIF-1 alpha. Given the similarity between morphogenesis o f the tracheal system and the vertebrate vascular system, the expressi on pattern of HRF in the vasculature and the bronchial tree raises the possibility that this family of transcription factors may be involved in tubulogenesis. (C) 1997 Elsevier Science Ireland Ltd.