Negative regulation of viral enhancers in undifferentiated embryonic stem cells.

Many viral genomes, including those of SV40 and MuLV, are not efficiently expressed in undifferentiated embryonal carcinoma (EC) cells but are expressed in differentiated derivatives. This regulation appears to be at the level of transcription. We have used DNA-mediated gene transfer to analyze the function of several viral promoters in EC cells. We show that the SV40 early promoter works efficiently in an enhancer-independent fashion following transfection into undifferentiated cells. Strikingly, the promoter in the LTR of MSV does not function in such cells; but when upstream sequences, including the enhancer, are deleted expression ensues. Replacement of the SV40 enhancer by that of MSV results in inactivation of the SV40 early promoter in these cells. We propose that the undifferentiated cells contain a trans-acting regulatory factor (or factors) that reduces transcription by interacting with viral enhancers.