The regulation of herpes simplex virus IE (immediate early) gene expression is mediated by the assembly of a multiprotein transcriptional enhancer complexes containing both cellular and viral proteins. This assembly provides a biochemically accessible model system for the analysis of DNA-protein and protein-protein interactions involved in the regulation of RNAPII directed transcription. Several of the proteins involved have been well characterized. However, the critical coordinator of the enhancer assembly (C1 factor), was only recently identified and purified. Therefore the primary objectives have been to determine the role of this protein in both viral and cellular processes. Analysis of the domains and interactions of the protein have indicated that the protein can be generally divided into regions which contain sequences for interactions with other cellular and viral transcription factors (mid-amino terminus) and the transcriptional activation domain (carboxy terminus). To assess the role of the C1 factor in cellular processes, various domains of the protein were used in two-hybrid screens. These screens were designed to isolate cellular proteins which interact with the C1 factor, providing information relative to its roles in different cellular functions. These screens yielded a number of mammalian cDNAs encoding both known and unknown proteins. Several of these are presently under investigation and include additional cellular trancription factors which are also involved in the expression of the HSV IE genes.
