Tissue-specific enhancer of the human glycoprotein hormone alpha-subunit gene: dependence on cyclic AMP-inducible elements.
We identified and characterized elements which confer tissue specificity and cyclic AMP (cAMP) responsiveness to the human glycoprotein alpha-subunit gene. An enhancer containing an 18-base-pair repeat conferred cAMP responsiveness in a non-tissue-specific fashion. DNase I protection assays revealed DNA-binding factors that bound to this element in both placental and nonplacental cells. It also enhanced the alpha-subunit promoter in a tissue-specific manner but had a negligible effect on a heterologous promoter. A unique element found upstream of this enhancer had no independent activity but, in combination with the cAMP-responsive enhancer, distinctly increased the tissue-specific activity of both the alpha-subunit promoter and a heterologous promoter. A factor that bound to this upstream element was found in placental but not nonplacental cells. We conclude that this novel element acts, perhaps through a specific trans-acting factor, in concert with a cAMP-responsive enhancer to confer tissue specificity to the alpha-subunit gene.
Delegeane
A M
AM
Regulatory Biology Laboratory, Salk Institute, La Jolla, California 92037.
Ferland
L H
LH
Mellon
P L
PL
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005796:Genes; D005809:Genes, Regulator; D006023:Glycoproteins / Q000235:genetics*; D006367:HeLa Cells / Q000502:physiology; D006728:Hormones / Q000235:genetics*; D006801:Humans; D046911:Macromolecular Substances; D009154:Mutation; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014162:Transfection
D006023:Glycoproteins; D006728:Hormones; D046911:Macromolecular Substances; D000242:Cyclic AMP