Mechanism of promoter selection by RNA polymerase II: Mammalian transcription factors α and βγ promote entry of polymerase into the preinitiation complex

Productive binding of RNA polymerase II at the core region of TATA box-containing promoters is controlled by the action of the TATA factor and four additional transcription factors, designated α, βγ, δ, and ε, which have each been purified to near homogeneity from rat liver. This process is accomplished in three distinguishable stages. In the first stage (initial complex formation), the core promoter is packaged with the TATA factor into a binary complex that serves as the recognition site for RNA polymerase II. Here we show that, in the second stage (site selection), transcription factors α and βγ act in combination to promote selective binding of RNA polymerase II to the initial complex. Several lines of evidence argue that α and βγ function at this stage by a mechanism related to that utilized by bacterial σ factors. In the third stage, transcription factors δ and ε promote assembly of the functional preinitiation complex. Our evidence supports the model that δ and ε enter the preinitiation complex and direct formation of stable protein-DNA contacts that anchor the transcription apparatus to the core promoter at sequences near the cap site.