Structural and functional analysis of coral Hypoxia Inducible Factor

Tissues of symbiotic Cnidarians are exposed to wide, rapid and daily variations of oxygen concentration. Indeed, during daytime, intracellular 02 concentration increases due to symbiont photosynthesis, while during night, respiration of both host cells and symbionts leads to intra-tissue hypoxia. The Hypoxia Inducible Factor 1 (HI F-1) is a heterodimeric transcription factor used for maintenance of oxygen homeostasis and adaptation to hypoxia. Here, we carried out a mechanistic study of the response to variations of 02 concentrations of the coral model Stylophora pistillata. In silico analysis showed that homologs of HIF-1 alpha (SpiHI F-1 alpha) and HIF-1 beta (SpiHI F-1 beta) exist in coral. A specific SpiHI F-1 DNA binding on mammalian Hypoxia Response Element (HRE) sequences was shown in extracts from coral exposed to dark conditions. Then, we cloned the coral HIF-1 alpha and 13 genes and determined their expression and transcriptional activity. Although HIF-1 alpha has an incomplete Oxygen dependent Degradation Domain (ODD) relative to its human homolog, its protein level is increased under hypoxia when tested in mammalian cells. Moreover, co-transfection of SpiH1F-1 a and p in mammalian cells stimulated an artificial promoter containing HRE only in hypoxic conditions. This study shows the strong conservation of molecular mechanisms involved in adaptation to 02 concentration between Cnidarians and Mammals whose ancestors diverged about 1,200-1,500 million years ago.