Induction of a factor that binds to the polyoma virus A enhancer on differentiation of embryonal carcinoma cells.

The cell type specificity of certain enhancers, competition experiments and the interactions that occur between proteins and enhancer sequences demonstrate that enhancers are the targets of specific factors involved in transcription control. The 246-base pair BclI-PvuII restriction enzyme fragment of polyoma virus has been shown to include two distinct enhancers, Py A and Py B, composed of several subdomains which interact with nuclear proteins from mouse fibroblasts. Embryonal carcinoma (EC) cells do not permit polyoma virus infection: both viral transcription and DNA replication are blocked. Host-range mutants of polyoma virus (EC mutants) capable of overcoming the expression block in EC cells have mutations or sequence rearrangements in their enhancer region. In an attempt to understand the molecular basis of this host restriction we compared the binding patterns displayed on the viral enhancer sequences by nuclear proteins prepared from EC cells or from fibroblasts. We show that one of the fibroblast factors required for Py A enhancer function, almost undetectable in EC cells, is induced after differentiation of these cells into parietal endoderm, suggesting that this protein is crucial in the regulation of viral gene expression during cellular differentiation, and perhaps more generally in the control of gene expression during early embryonic development.