Cloning of a human DNA sequence that restores expression of hepatic functions in a dedifferentiated rat hepatoma cell.

In a study of the regulation of gene expression in liver cells, a strain of dedifferentiated cells (C2) derived from the rat hepatoma line H4IIEC3 was transfected with DNA from human liver. After growth of these C2 variants in a glucose-free medium, revertants were selected which were characterized by the expression of a complete set of liver functions. A 4.3 kb human DNA sequence was detected with an Alu sequence probe in cells of four independent revertant clones and was shown to be an extrachromosomal, covalently closed duplex DNA. This molecule, called HALF1 for reversion inducing sequence, was cloned and transfected into C2 cells. Analyses of the transfectants indicated a correlation between the introduction of this cloned genomic human DNA sequence and the recovery of hepatic traits.