The punctilious RNA polymerase II core promoter

Abstract

The signals that direct the initiation of transcription ultimately converge at the core promoter, which is the gateway to transcription. Here we provide an overview of the RNA polymerase II core promoter in bilateria (bilaterally symmetric animals). The core promoter is diverse in terms of its composition and function yet is also punctilious, as it acts with strict rules and precision. We additionally describe an expanded view of the core promoter that comprises the classical DNA sequence motifs, sequence-specific DNA-binding transcription factors, chromatin signals, and DNA structure. This model may eventually lead to a more unified conceptual understanding of the core promoter.

Keywords: RNA polymerase II; TBP; TBP-related factors; chromatin; core promoter; core promoter elements; sequence-specific transcription factors.

Figure 1.

Focused, dispersed, and mixed transcription initiation patterns. In focused transcription, there is either a single predominant TSS or a narrow cluster of TSSs that probably derive from a single PIC. In dispersed transcription, there are multiple weak TSSs spread over an ∼50- to 100-base-pair (bp) region that likely emanate from multiple PICs. Focused and dispersed transcription patterns are two endpoints of a spectrum of possible mechanisms, and a variety of mixed TSS patterns are commonly observed. TSS patterns are also known as promoter shape.

Figure 2.

A plethora of core promoter sequence motifs for RNA Pol II. A typical core promoter might have zero to three of the indicated core promoter elements. The locations of the sequence motifs are roughly to scale. The consensus sequences are listed in Table 1.

Figure 3.

Enhancer–core promoter specificity. This diagram depicts transcriptional enhancers that function selectively with DPE-dependent or TATA-dependent core promoters (Butler and Kadonaga 2001; Juven-Gershon et al. 2008b). Enhancer–core promoter specificity has also been observed with a developmental core promoter (with TATA, Inr, MTE, and DPE motifs) versus a housekeeping core promoter (with the TCT motif) (Zabidi et al. 2015). (Adapted from Butler and Kadonaga 2001.)

Figure 4.

Transcriptional programs that are directed by TBP, TRF1, and TRF2 in Drosophila. This diagram shows the partitioning of transcriptional functions between TBP, TRF1, and TRF2 in Drosophila. It appears that each of these system factors is responsible for a set of transcriptional programs. As discussed in the text, humans lack TRF1 and contain TBP, TRF2, and TRF3. Moreover, in humans, the specific functions of factors such as TRF2 remain to be clarified. (Adapted from Duttke et al. 2014.)

Figure 5.

A model for divergent transcription. In this model, a promoter region that exhibits divergent transcription contains a unidirectional forward core promoter and a unidirectional reverse core promoter that flank binding sites for sequence-specific transcription factors.

Figure 6.

Potential functions of sequence-specific DNA-binding transcription factors and chromatin signals at the core promoter. (A) Postulated role of SSTFs in core promoter function. In this model, SSTF-binding sites in the immediate upstream promoter region (∼50–80 bp upstream of the TSS) function in a manner that is analogous to a TATA box. Thus, the combination of an SSTF-binding site and an Inr could act as a core promoter. (B) A composite of the potential role of chromatin signals and structure in core promoter function. It may be necessary to analyze the core promoter in the broader context of chromatin. Examples discussed in the text include the following. H3K4me3 has been found to recruit TFIID via its TAF3 subunit (Vermeulen et al. 2007; Lauberth et al. 2013). Salt-labile nucleosomes containing the histone variants H2A.Z and H3.3 have been found at active chromatin (Jin et al. 2009). The prenucleosome, a conformational isomer of the nucleosome that interacts with ∼80-bp DNA, appears to be present in the immediate upstream region of active promoters (Fei et al. 2015; Khuong et al. 2015). In plants, RNA Pol V is recruited to promoters via methylated DNA (Johnson et al. 2014; Liu et al. 2014). Although CpG methylation is generally repressive in vertebrates, DNA modifications such as methylation or hydroxymethylation may also function as a positive signal for the initiation of Pol II transcription.