Interaction of trans-acting factors and re-expression of liver functions in hepatoma hybrid cells.

Abstract

The specific functions expressed by differentiated cells are extinguished when these cells are crossed with somatic cells of another histotype or with cells of the same differentiation that fail to express these functions: in rat hepatoma x mouse fibroblast hybrids, tyrosine aminotransferase (TAT) and phosphoenolypyruvate carboxykinase (PEPCK) activities are extinguished as they are in hybrids between the same rat hepatoma cell line and mouse hepatoma cells that do not express these two enzymes. The locus Tse-1 (tissue-specific extinguisher) on mouse chromosome 11 is responsible for the extinction of TAT and PEPCK in rat hepatoma x mouse fibroblast hybrids and loss of mouse chromosome 11 leads to re-expression of these two enzymes. We report here an analysis of rat hepatoma x mouse hepatoma hybrids that demonstrates that loss of mouse chromosome 11 is not necessary for re-expression of TAT and PEPCK. In view of the facts that Tse-1 is active in mouse hepatoma cells that do not express TAT and PEPCK and that the presence of only one active Tse-1 locus is sufficient to extinguish these functions in 2s rat hepatoma cells, we conclude that re-expression of TAT and PEPCK in rat hepatoma x mouse hepatoma hybrids is due to the epistatic action of tissue-specific trans-acting activators that override the Tse-1 effect.