Hypoxia-sensitive domain in the human cytosolic phospholipase A2 promoter

Transcription from the human cytosolic phospholipase A(2) gene has been observed to be hypoxia sensitive in endothelial cells cultured from the human cerebral microvasculature. DNA sequence analysis of the cytosolic phospholipase A2 promoter revealed the presence of a distal cluster of potential hypoxia-inducible factor-I-DNA binding sites homologous to 5'-NCGTG-3', located between -1087 and -996 bp of the major start of transcription at + I bp (Genbank U08374). Gel shift assay showed strong hypoxia-inducible factor-I-DNA binding to only a single site within this cluster, and promoter deletion analysis indicated the functional importance of this chromatin domain in conveying oxygen sensitivity to cytosolic phospholipase A(2) gene transcription. Non-functional hypoxia inducible factor-I-DNA binding sites flanking a single functional hypoxia-inducible factor-I-DNA binding site in this hypoxia-sensitive domain may promote oxygen sensitivity via transcription factor clustering or Circe effects.