HNF4 AND HNF1 AS WELL AS A PANEL OF HEPATIC FUNCTIONS ARE EXTINGUISHED AND REEXPRESSED IN PARALLEL IN CHROMOSOMALLY REDUCED RAT HEPATOMA-HUMAN FIBROBLAST HYBRIDS

Rat hepatoma-human fibroblast hybrids of two independent lineages cont aining only 8-11 human chromosomes show pleiotropic extinction of thir teen out of fifteen hepatic functions examined. Reexpression of the en tire group of functions most often occurs in a block, and except for o ne discordant subclone, correlates with loss of human chromosome 2. Th e extinguished cells and their reexpressing derivatives have been exam ined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically ex tinguished in parallel with the hepatic functions. However, HNF1 and H NF4 show a perfect correlation with phenotype: these factors are expre ssed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be propo sed that the HNF4 gene is the primary target of the pleiotropic exting uisher.