Analysis of the Promoter Region of the Human VEGF-Related Factor Gene

We have characterised the promoters of the human and murineVRF(vascular endothelial growth factor (VEGF) related factor) gene. A series of deletions were made of a 553-bp region 5′ of theVRFinitiation codon and were used in a luciferase reporter gene assay to determine the minimal promoter of theVRFgene. The region between base pairs −443 and −195 was sufficient to mediate transcription in lymphocytes and the region between −550 and −443 enhanced this promoter activity. Primer extension studies identified two regions of transcription initiation, both of which are preceded by Sp1, AP-2 and Egr-1 transcription factor binding sites. TheVRFpromoter is similar toVEGFin that it is associated with a CpG island, contains sites for Sp1 and AP-2, and lacks a TATA box. However, it has marked differences in that the promoter contains Egr-1 sites and lacks both hypoxia-inducible factor-1 and AP-1 sites. These data may indicate that expression of these two growth factors is regulated by different physiological stimuli.