A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development

• DOI: 10.1073/pnas.94.9.4273
• Publication Date: 2002-07-26T14:31:39Z
• Authors: Masatsugu Ema; Shinichiro Taya; Noboru Yokotani; Kazuhiro Sogawa; Youichi Matsuda; Yoshiaki Fujii-Ku...
• Keywords: Hypoxia-Inducible Factors

We have isolated and characterized a cDNA for novel Per-Arnt/AhR-Sim basic helix–loop–helix (bHLH-PAS) factor that interacts with the Ah receptor nuclear translocator (Arnt), its predicted amino acid sequence exhibits significant similarity to hypoxia-inducible 1α (HIF1α) Drosophila trachealess ( dTrh ) gene product. The HIF1α-like (HLF) encoded by bound hypoxia-response element (HRE) found in enhancers of genes erythropoietin, vascular endothelial growth (VEGF), various glycolytic enzymes, activated transcription reporter harboring HRE. Although transcription-activating properties HLF were very similar those reported HIF1α, their expression patterns quite different between two factors; mRNA was most abundantly expressed lung, followed heart, liver, other organs under normoxic conditions, whereas HIF1α ubiquitously at much lower levels. In lung development around parturition, markedly enhanced, remained apparently unchanged level. Moreover, closely correlated VEGF mRNA. Whole mount situ hybridization experiments demonstrated cells middle stages (9.5 10.5 days postcoitus) mouse embryo development, where almost undetectable. high level O 2 delivery system developing embryos adult suggests state, regulates VEGF, others driven HRE sequence, may be involved blood vessels tubular lung.