HIF1A gene transcription is dependent on a core promoter sequence encompassing activating and inhibiting sequences located upstream from the transcription initiation site and cis elements located within the 5 ' UTR

Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of tw o subunits, HIF-1 alpha and ARNT, which is activated under hypoxia. HIF-1 a lpha mRNA is expressed constitutively in a wide variety of cell types, wher eas in some others HIF1A gene expression is upregulated by hypoxia. In this report, we show that in endothelial cells (HMEC-1) the HIF-1 alpha mRNA ex pression level is the same in both normoxia and hypoxia. Deletion analysis experiments of the HIF1A promoter showed that in hypoxia HIF1A gene express ion is upregulated through a short sequence located next to the transcripti on initiation site. We also show that in hypoxia another sequence located u pstream from the +1 initiation site plays an inhibitory role on HF1A transc ription in HMEC-1 but not in hepatoma cells and brings back this expression level to that observed in normoxia. Finally, we demonstrate that HIF1A gen e transcription is dependent on Sp1 binding sites and that the 5'UTR sequen ce also contains other important cis-acting elements. (C) 1999 Academic Pre ss.