The RNA polymerase II core promoter - the gateway to transcription

Abstract

The RNA polymerase II core promoter is generally defined to be the sequence that directs the initiation of transcription. This simple definition belies a diverse and complex transcriptional module. There are two major types of core promoters - focused and dispersed. Focused promoters contain either a single transcription start site or a distinct cluster of start sites over several nucleotides, whereas dispersed promoters contain several start sites over 50-100 nucleotides and are typically found in CpG islands in vertebrates. Focused promoters are more ancient and widespread throughout nature than dispersed promoters; however, in vertebrates, dispersed promoters are more common than focused promoters. In addition, core promoters may contain many different sequence motifs, such as the TATA box, BRE, Inr, MTE, DPE, DCE, and XCPE1, that specify different mechanisms of transcription and responses to enhancers. Thus, the core promoter is a sophisticated gateway to transcription that determines which signals will lead to transcription initiation.

Figure 1

Focused versus dispersed core promoters. In focused core promoters, transcription initiates at a single site or in a cluster of sites in a narrow region of several nucleotides. Dispersed core promoters are typically found in CpG islands in vertebrates and usually yield multiple weak start sites over a region of 50 to 100 nucleotides. Focused core promoters are more ancient and widespread throughout nature than dispersed core promoters. In vertebrates, however, dispersed promoters are more common than focused promoters. There may be fundamental differences in the basic mechanisms of transcription from focused versus dispersed core promoters.

Figure 2

Core promoter motifs. This diagram, which is drawn roughly to scale, shows some of the known core promoter elements for transcription by RNA polymerase II. There are no universal core promoter elements. Each of these elements is found in only a fraction (typically estimated to be from 1% to 30%, depending on the motif) of all core promoters. The Inr is probably the most commonly occurring core promoter motif. There are additional core promoter elements that remain to be discovered. The TATA box, Inr, MTE, DPE, and DCE are recognition sites for the binding of transcription factor TFIID. It should be noted, however, that there are multiple forms of TFIID and TFIID-related protein complexes that could potentially interact with the core promoter. BRE^u and BRE^d interact with TFIIB.