ENDOGENOUS AND TRANSFECTED MOUSE ALPHA-FETOPROTEIN GENES IN UNDIFFERENTIATED F9 CELLS ARE ACTIVATED IN TRANSIENT HETEROKARYONS

Mouse F9 teratocarcinoma cells provide a system to study developmental ly regulated alpha-fetoprotein (AFP) gene expression. AFP is not expre ssed in undifferentiated F9 cells but is induced when cells differenti ate as cell aggregates in the presence of retinoic acid. Previous stud ies have led to the suggestion that undifferentiated F9 cells contain negative regulators of AFP expression. To test this, we have used tran sient heterokaryons to ask whether inactive AFP genes in undifferentia ted F9 cells are responsive to positively acting trans-acting factors. Our results indicate that silent endogenous and transfected AFP genes are activated when undifferentiated F9 cells are fused to human hepat oma HepG2 cells. This suggests that the lack of AFP expression in undi fferentiated F9 cells is due to the absence or insufficient level of p ositive-acting transcription factors, rather than the presence of domi nant negative regulators. We also demonstrate that stably transfected AFP genes, although unmethylated, are properly regulated in F9 cells.