title: Regulation of chimeric phosphoenolpyruvate carboxykinase genes by the trans-dominant locus TSE1.
abstract: Extinction of phosphoenolpyruvate carboxykinase (PCK) gene expression in hepatoma x fibroblast hybrids is mediated by a trans-acting genetic locus designated tissue-specific extinguisher 1 (TSE1). To identify PCK gene sequences required for extinction, hepatoma transfectants expressing PCK-thymidine kinase (TK) chimeric genes were fused with TK- fibroblasts and PCK-TK expression in the resulting hybrids was monitored. Expression of a PCK-TK chimera containing PCK sequences between base pairs -548 and +73 was extinguished in four of five hepatoma transfectants tested, although hybrids derived from one transfectant clone failed to extinguish PCK-TK expression. In contrast, crosses between hepatoma transfectants expressing the herpesvirus TK gene from its own promoter and TK- fibroblasts produced TK+ hybrids; extinction of the transfected TK gene was not observed. Thus, rat PCK gene sequences between base pairs -548 and +73 are sufficient for tissue-specific extinction in hybrid cells. Extinction of PCK-TK gene expression in transfectant microcell hybrids mapped specifically to human chromosome 17, the site of human TSE1.
authors.affiliation: Department of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
authors.forename: M J
authors.initials: MJ
authors.lastname: Thayer
authors.forename: T G
authors.initials: TG
authors.lastname: Lugo
authors.forename: R J
authors.initials: RJ
authors.lastname: Leach
authors.forename: R E
authors.initials: RE
authors.lastname: Fournier
mesh_terms: D000818:Animals; D002460:Cell Line; D002678:Chimera; D002872:Chromosome Deletion; D005786:Gene Expression Regulation; D005796:Genes; D005799:Genes, Dominant; D006822:Hybrid Cells / Q000201:enzymology; D015151:Immunoblotting; D007739:L Cells / Q000201:enzymology; D051379:Mice; D009693:Nucleic Acid Hybridization; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000201:enzymology
chemical_list: D013937:Thymidine Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)