The Start Point for RNA Polymerase II

KEY CONCEPTS
- RNA polymerase II requires general transcription factors (TF_II X) to initiate transcription.
- RNA polymerase II promoters frequently have a short conserved sequence, Py₂ CAPy₅ (the initiator, Inr), at the start point.
- The TATA box is a common component of RNA polymerase II promoters; it consists of an A-T–rich octamer located approximately 25 bp upstream of the start point.
- The downstream promoter element (DPE) is a common component of RNA polymerase II promoters that do not contain a TATA box.
- A core promoter for RNA polymerase II includes the Inr and, commonly, either a TATA box or a DPE. It may also contain other minor elements.
The basic organization of the apparatus for transcribing proteincoding genes was revealed by the discovery that purified RNA polymerase II can catalyze synthesis of mRNA, but that it cannot initiate transcription unless an additional extract is added. The purification of this extract led to the definition of the general transcription factors, or basal transcription factors—a group of proteins that are needed for initiation by RNA polymerase II at all promoters. RNA polymerase II in conjunction with these factors constitutes the basal transcription apparatus that is needed to transcribe any promoter. The general factors are described as TF_II X, where X is a letter that identifies the individual factor. The subunits of RNA polymerase II and the general transcription factors are conserved among eukaryotes.
Our starting point for considering promoter organization is to define the core promoter as the shortest sequence at which RNA polymerase II can initiate transcription. A core promoter can, in principle, be expressed in any cell (though in practice a core promoter alone results in little or no transcription in the chromatin context in vivo). It is the minimum sequence that enables the general transcription factors to assemble at the start point. These factors are involved in the mechanics of binding to DNA and enable RNA polymerase II to recognize the promoter and initiate transcription. A core promoter functions at only a low efficiency.
Other proteins, called activators, a different class of transcription factors, are required for the proper level of function . The activators are not described systematically, but have casual names reflecting their histories of identification.
We might expect any sequence components involved in the binding of RNA polymerase and general transcription factors to be conserved at most or all promoters, as is the case for pol I and pol III promoters. As with bacterial promoters, when promoters for RNA polymerase II are compared homologies in the regions near the start point are restricted to rather short sequences. These elements correspond with the sequences implicated in promoter function by mutation. FIGURE 1 shows the construction of a typical pol II core promoter with three of the most common pol II promoter elements. However, the eukaryotic pol II promoter is far II more structurally diverse than the bacterial promoter and the promoters for pol I and III. In addition to the three major elements, a number of minor elements can also serve to define the promoter.

FIGURE 1. A minimal pol II promoter may have a TATA box ~25 bp upstream of the Inr. The TATA box has the consensus sequence of TATAA. The Inr has pyrimidines (Y) surrounding the CA at the start point. The DPE is downstream of the start point. The sequence shows the coding strand.
The start point does not have an extensive homology of sequence, but there is a tendency for the first base of mRNA to be A, flanked on either side by pyrimidines. (This description is also valid for the CAT start sequence of bacterial promoters.) This region is called the initiator (Inr), and it may be described in the general form Py₂CAPy₅ , where Py stands for any pyrimidine. The Inr is contained between positions −3 and +5.
Many promoters have a sequence called the TATA box, usually located approximately 25 bp upstream of the start point in higher eukaryotes. It constitutes the only upstream promoter element that has a relatively fixed location with respect to the start point. The consensus sequence of this core element is TATAA, usually followed by three more A-T base pairs .
The TATA box tends to be surrounded by G-C–rich sequences, which could be a factor in its function. It is almost identical with the sequence of the −10 box found in bacterial promoters; in fact, it could pass for one except for the difference in its location at −25instead of −10. (The exception is in yeast, where the TATA box is  more typically found at −90.) Single-base substitutions in the TATA box may act as up or down mutations, depending on how closely the original sequence matches the consensus sequence and how different the mutant sequence is. Typically, substitutions that introduce a G-C base pair are the most severe.
Promoters that do not contain a TATA element are called TATAless promoters. Surveys of promoter sequences suggest that 50% or more of promoters may be TATA-less. When a promoter does not contain a TATA box, it often contains another element, the downstream promoter element (DPE), which is located at +28 to +32 within the transcription unit.
Typical core promoters consist either of a TATA box plus Inr or of an Inr plus DPE, although other combinations with minor elements exist as well.

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