EIa-mediated transactivation of the adenovirus EIIa early promoter is restricted in undifferentiated F9 cells.

The murine embryonal carcinoma (EC) F9 cells express an adenovirus EIa-like activity which is abolished after differentiation of these cells. We have examined the ability of the adenovirus EIa gene products to transactivate the viral early EIIa (EIIaE) promoter in this cell system. Surprisingly, as shown both by infection and transfection experiments, the EIIaE promoter was refractory to viral EIa-mediated activation in the undifferentiated F9 EC cells, EIa-responsiveness being recovered only after differentiation of these cells. This EC-cell-specific restriction did not correspond to a lack of EIa gene expression, nor to a deficiency of any of the major transcription factors involved in EIIaE basal promoter activity. In these differentiated F9 cells, EIIaE promoter activation correlates with a modification of E2F resulting in its ability to cooperatively interact with the promoter. Our observation that such a modification neither occurs in uninfected F9 EC cells (Jansen-Durr et al., 1989, EMBO J., 8, 3365), nor at early times after infection of these cells suggests that a viral product is required together with the EIa-like activity to induce this modification of E2F. The implication of an EIV gene product in this effect is discussed.