Differential and opposed transcriptional effects of protein fusions containing the VP16 activation domain.

Overexpression of strong transcriptional activators like herpes simplex virion protein 16 (VP16) may lead to non-specific inhibition of gene expression as a result of the titration of transcription factors. Here we report that a fusion between the homeoprotein Hoxa2 and the VP16 activation domain inhibits transcription from the strong promoter/enhancers of cytomegalovirus (CMV) and Rous sarcoma virus (RSV). A similar fusion involving a Hoxa2 mutant protein that is defective in DNA binding has no effect on the CMV promoter but increases, rather than inhibits, the RSV promoter activity. This suggests that depending on its ability to bind DNA, the VP16 activator can interact with different sets of cofactors, giving rise to distinct transcriptional effects.