Pituitary-specific repression of placental members of the human growth hormone gene family. A possible mechanism for locus regulation
Autor: | M W, Nachtigal, B E, Nickel, P A, Cattini |
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Rok vydání: | 1993 |
Předmět: |
Binding Sites
Base Sequence Placenta Molecular Sequence Data Oligonucleotides DNA Regulatory Sequences Nucleic Acid Rats Repressor Proteins Gene Expression Regulation Organ Specificity Growth Hormone Multigene Family Pituitary Gland Tumor Cells Cultured Animals Humans Pituitary Neoplasms Placental Hormones |
Zdroj: | The Journal of biological chemistry. 268(12) |
ISSN: | 0021-9258 |
Popis: | Five members of the human growth hormone (GH) gene family are located at a single locus on chromosome 17. Growth hormone is expressed in the pituitary under the control of the tissue-specific factor Pit 1/GHF-1, and chorionic somatomammotropin (CS) -A, -B, and -L, as well as placental GH variant, are expressed specifically in the placental syncytiotrophoblast. Despite this specificity in vivo, the CS-A promoter can bind Pit 1/GHF-1 and allow CS-A promoter activity in pituitary tumor cells after gene transfer. We have identified and characterized PSF sequences associated with only the placental members in the GH/CS locus which repress placental promoter activity90% in transfected pituitary cells. These sequences do not significantly affect promoter function in placental cells after gene transfer. Repressor activity correlates with binding of protein at two sites (PSF-A and PSF-B) with pituitary, but not placental, nuclear extracts. Competition studies suggest an interaction between PSF and Pit 1/GHF-1 proteins. These results indicate that PSF protein can repress CS-A promoter activity in a tissue-specific manner in vitro and provide a possible mechanism by which expression of placental members of the GH family are inhibited in the pituitary in vivo. |
Databáze: | OpenAIRE |
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