Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism.

We have constructed retrovirus vectors containing two genes, each with its own promoter, whose products can be selected in vivo. In cell clones harboring a single copy of this bicistronic provirus, we find that the 3' gene is usually suppressed when there is selection for expression of the 5' gene, and the 5' gene is usually suppressed when there is selection for expression of the 3' gene. We find that the suppression is epigenetic, reversible, and cis-acting, and is influenced by the strength or position of the different promoters. This type of gene suppression is novel for its action on a gene that can be either upstream or downstream to an adjacent active gene.