A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells.

Hybrid cells formed by fusing different cell types generally fail to express the tissue-specific products of either parent, a phenomenon termed extinction. We have investigated the generality of this effect by assaying hepatoma-fibroblast hybrids for expression of 16 different liver-specific mRNAs. Fourteen of the mRNAs failed to accumulate in karyotypically complete hybrid clones, and quantitative measurements indicated that steady-state mRNA levels were depressed by a factor of at least 500-1000. However, all 14 liver-specific mRNAs were reexpressed in the hybrids following fibroblast chromosome loss. These data indicate that expression of whole sets of tissue-specific genes is affected in trans in intertypic hybrids and suggest that negative regulation of heterologous functions may be common form of gene control.