The 5′-Flanking Sequences of the Human Growth Hormone Gene Contain a Cell-Specific Control Element

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Abstract
The 5′-flanking sequences of the human growth hormone (hGH) gene contain a cell-specific control element. Hybrid genes containing truncated 5′-flanking DNA fragments from the hGH gene fused to the chloramphenicol acetyl transferase (cat) gene were examined using transient transfection of rat anterior pituitary (GC) and nonpituitary cell lines (HeLa, Rat 2, and KB); preferential expression of these gene hybrids was only observed in GC cells. Deletions through the 5′-flanking sequences of the hGH gene revealed that the region containing nucleotides -230 to -180 is required for efficient cat gene expression in GC cells. This region of DNA is highly homologous to a region of the rGH gene that contains a tissue-specific control element. A hybrid gene containing the tissue-specific control element, but lacking the proximal promoter elements, of the hGH gene upstream from the promoter of the thymidine kinase gene (TKp) from herpes simplex virus ligated to the cat gene produced more CAT activity than the TKp.cat gene in GC cells but not in HeLa cells. These data suggest that the tissue-specific control element located in the 5′-region of the hGH gene can act in the presence of a heterologous promoter and is specific for expression in pituitary cells.