INDUCTIVE EFFECT OF A HUMAN DNA-SEQUENCE (HALF1) ON THE DIFFERENTIATION OF A VARIANT RAT HEPATOMA-CELL (C2) IS RESTRICTED TO EPISOMAL FORMSOF THE MOLECULE

HALF1, a 4.3 kb human DNA sequence, was originally identified as a dou ble-stranded, closed-circular DNA molecule in revertants from a dediff erentiated rat hepatoma cell (C2) transfected with human liver DNA. He re we report its specific properties in inducing the transition to the hepatic phenotype. (i) In vitro recircularized HALF1 induces reversio n after a minimum time lag of 7 days post-transfection. (ii) After ind uction, the presence of HALF1 is not required for maintaining the indu ced hepatic state. (iii) HALF1 is detected as a sequence integrated in high molecular mass DNA of human liver. (iv) HALF1 monomer or dimer p lasmid constructs do not induce reversion when integrated into the gen ome of transfectants. (v) Short ubiquitous RNA transcripts (similar to 400 bases) are detected with specific HALF1 probes. These results ind icate that the reversion process is linked to the presence of HALF1 ex trachromosomal molecules.