Pituitary-specific repression of placental members of the human growth hormone gene family. A possible mechanism for locus regulation.
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 activity > 90% 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.
Nachtigal
M W
MW
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Nickel
B E
BE
Cattini
P A
PA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009841:Oligonucleotides; D009928:Organ Specificity / Q000235:genetics; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms; D010920:Placenta / Q000378:metabolism*; D010926:Placental Hormones / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C064980:GH2 protein, human; D009841:Oligonucleotides; D010926:Placental Hormones; D012097:Repressor Proteins; D013006:Growth Hormone; D004247:DNA