Accumulation of p300 mediates transcriptional repression of simian virus 40 enhancer in undifferentiated F9 embryonal carcinoma cells.

The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiated EC cells and that the levels decline dramatically upon differentiation because of the changes of protein stability. Furthermore, we showed that overexpression of p300 does not stimulate the SV40 enhancer activity in undifferentiated F9 cells. However, the activity of a p300 mutant deficient for E1A binding can be restored by the presence of excess E1A. In addition, low-level expression of E1A causes derepression of the enhancer activity in F9 cells. These results indicate that the accumulation of p300 protein participates in repression of the SV40 enhancer activity in undifferentiated F9 cells.