Chromosomal position or virus mutation permits retrovirus expression in embryonal carcinoma cells

Retrovirus expression is restricted in embryonal carcinoma (EC) cells. To study how a virus can overcome this block, we selected and analyzed rare proviruses that are expressed in F9 cells. Our results indicate that provirus expression occurs by two different mechanisms: one provirus acquired a single base pair mutation in the retrovirus tRNA primer binding site, permitting provirus expression; expression of three proviruses was mediated by 5′-flanking DNA sequences. Surprisingly, five proviruses in 17 selected cell lines integrated into the same two distinct chromosomal regions, suggesting that the number of chromosomal positions in the cellular genome that allows virus expression is very limited. Our results suggest that genomic sequences that are actively transcribed in EC cells can be isolated by selection for retrovirus expression.