STRUCTURAL ORGANIZATION AND THE TRANSCRIPTION INITIATION SITE OF THE HUMAN HEPATOCYTE GROWTH-FACTOR GENE

The structural organization of the gene coding for human hepatocyte growth factor (hHGF) has been determined by seven overlapping-lambda-phage genomic clones including three clones that were previously characterized. The gene for hHGF spans about 70 kbp of DNA and consists of 18 exons separated by 17 introns. The coding sequence of hHGF consists of multiple putative domains that are homologous to those observed in plasminogen. These regions were found as separate exons in the gene, and the exon-intron arrangement was similar to that of plasminogen. These results suggest that the genes for hHGF and plasminogen have arisen through gene duplication events from an ancestral gene. The major transcription initiation site of the hHGF gene is located 76 bp upstream of the translational start codon as judged by S1 nuclease mapping and primer extension analyses. A TATA-like element was found 33 nucleotides upstream of the transcription initiation site. Two sequence elements, an interleukin 6 response element (CTGGGA) and a potential binding site for NF-IL6 (TGAGGAAAG), are located near the transcription initiation site. These sequence elements might be involved in the regulation of HGF gene expression.