Human placental lactogen transcriptional enhancer. Tissue specificity and binding with specific proteins

Human placental lactogen (hPL) and growth hormone (hGH) are thought to be derived from a common ancestral gene and have similar nucleotide and amino acid sequences. Although the genes are similar in structure, they are expressed in different tissues. A transcriptional enhancer has been found 2.2 kilobases 3' of the hPL3 gene at the distal extreme of the hPL/hGH gene cluster. This enhancer is at least 20-fold more active in hPL-producing human choriocarcinoma JEG-3 cells than in non-hPL-producing cells. The enhancer is active when linked to either the hPL3 or SV40 promoter. We have localized the hPL enhancer to a 138-base pair (bp) region that retains tissue specificity in transient transfection assays. Gel mobility shift assays showed that the hPL enhancer interacted specifically with nuclear proteins from JEG-3 cells and placental tissue. Within the 138-bp enhancer, a 22-bp region overlapping a TEF-1 binding site was shown to be protected from DNase I digestion by placental and HeLa nuclear extracts. Placental protein(s) binding this region may be instrumental in tissue-specific activity of the hPL enhancer.