Differential regulation of viral and cellular genes in F9 mouse embryonal carcinoma cells.

Expression of genes driven by the SV40 promoter/enhancer appears to be under net negative regulatory control in undifferentiated F9 cells, but not in their differentiated derivatives. In cells containing integrated copies of an SV40 promoter-driven marker gene, induction of differentiation by retinoic acid treatment produced a modest increase in transcription from the viral promoter. A much greater increase was observed when differentiated or undifferentiated cells were treated with the protein synthesis inhibitor, cycloheximide. If cycloheximide acts through removal of negative-regulatory molecule(s), then it is apparent that these molecules are present in both differentiated and undifferentiated cells, and that retinoic acid treatment removes only a portion of the total transcriptional repression. RNA levels from a variety of cellular genes activated during F9 cell differentiation were either unaffected or only slightly increased by cycloheximide treatment. This suggests important qualitative or quantitative differences in the regulation mechanism for viral and cellular genes in differentiating F9 cells.