The basal initiation machinery: beyond the general transcription factors

Abstract

In vitro experiments led to a simple model in which basal transcription factors sequentially assembled with RNA Polymerase II to generate a preinitiation complex (PIC). Emerging evidence indicates that PIC composition is not universal, but promoter-dependent. Active promoters are occupied by a mixed population of complexes, including regulatory factors such as NC2, Mot1, Mediator, and TFIIS. Recent studies are expanding our understanding of the roles of these factors, demonstrating that their functions are both broader and more context dependent than previously realized.

Figure. Many Paths to the PIC

The factors and assembly pathways used to form transcriptionally competent preinitiation complexes can be promoter dependent [3,73]. 1) TBP assembling onto promoter regions via TFIID leads to recruitment of the other basal initiation factors, as outlined in the stepwise assembly pathway [1]. In S. cerevisiae, this pathway is most often utilized at TATA-less genes. At some mammalian promoters, histone H3K4 trimethylation helps to recruit the TFIID complex [5]. 2) Mediator bridges interactions between activators and the basal initiation machinery, and can stimulate basal transcription as well. At some promoters Mediator can recruit TFIIH and TFIIE independently of RNApII [45]. 3) TBP can also be brought to promoters by the SAGA complex. In S. cerevisiae, this pathway is most utilized at TATA containing promoters. The Mot1 and NC2 complexes can repress this pathway by actively removing TBP from the TATA element [73]. 4) Mot1 and NC2 can also have a positive role in transcription by removing nonproductive TBP complexes from DNA, thereby allowing functional PICs to form [60,65,77].