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
G. Griffo et al., 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, The Journal of cell biology, 121(4), 1993, pp. 887-898
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.