Hormonal regulation of TSE1-repressed genes: evidence for multiple genetic controls in extinction.
Somatic cell hybrids formed by fusing hepatoma cells with fibroblasts generally fail to express liver functions, a phenomenon termed extinction. Previous studies demonstrated that extinction of the genes encoding tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and argininosuccinate synthetase is mediated by a specific genetic locus (TSE1) that maps to mouse chromosome 11 and human chromosome 17. In this report, we show that full repression of these genes requires a genetic factor in addition to TSE1. This conclusion is based on the observation that residual gene activity was apparent in monochromosomal hybrids retaining human TSE1 but not in complex hybrids retaining many fibroblast chromosomes. Furthermore, TSE1-repressed genes were hormone inducible, whereas fully extinguished genes were not. Analysis of hybrid segregants indicated that genetic loci required for the complete repression phenotype were distinct from TSE1.
Thayer
M J
MJ
Department of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Fournier
R E
RE
D000818:Animals; D001124:Argininosuccinate Synthase / Q000235:genetics*; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002886:Chromosomes, Human, Pair 17; D000242:Cyclic AMP / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D015342:DNA Probes; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006728:Hormones / Q000502:physiology*; D006801:Humans; D006822:Hybrid Cells; D008025:Ligases / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D014444:Tyrosine Transaminase / Q000235:genetics*
D015342:DNA Probes; D006728:Hormones; D012333:RNA, Messenger; D003994:Bucladesine; D003907:Dexamethasone; D004247:DNA; D003513:Cycloheximide; D000242:Cyclic AMP; D014444:Tyrosine Transaminase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D008025:Ligases; D001124:Argininosuccinate Synthase