[14] Nuclear RNA polymerases: Role of general initiation factors and cofactors in eukaryotic transcription

This chapter reviews some of the many factors that function in the three RNA polymerase systems, referring to studies in eukaryotes ranging from yeast to mammalian cells. It is clear that significant advances have made it possible to study fundamental transcription mechanisms in systems reconstituted with highly purified RNA polymerases and general transcription factors, many of which are available as functional recombinant proteins. Further, systems of variable purity can be used to study the mechanism of action of gene-specific activators, most notably with model promoters and activators. However, a major challenge will be to extend the analyses to natural promoters and activators, as well as to natural chromatin templates; and this will undoubtedly demand the identification, purification, and characterization of still other (co)factors—at least in the Pol II systems. In addition, the identification of multicomponent complexes of RNA polymerases, general factors, and cofactors necessitates that the physiological relevance of these complexes be further investigated and that the preinitiation complex assembly and activation pathways worked out with isolated components be evaluated accordingly.