Tissue-specific expression of hepatic functions. Genetic aspects

Intertypic hybrids formed by fusing dissimilar cell types generally fail to express the tissue-specific products of either parent, a phenomenon termed extinction. To explore the genetic basis and phenotypic complexity of this phenomenon, 15 liver-specific cDNA clones have been used as probes to assay expression of the corresponding mRNAs in a series of hepatoma x fibroblast hybrids retaining different fibroblast chromosomes. Thirteen of the 15 liver-specific mRNAs were extinguished in karyotypically complete hepatoma x fibroblast hybrids, but were reexpressed in hybrid segregants that had eliminated fibroblast chromosomes. In three cases analyzed in detail, extinction of a particular hepatic marker required the presence of a single, specific fibroblast chromosome. These data define and localize a set of discrete genetic loci, the Tse loci, that negatively regulate liver-specific gene expression in trans.