Core promoter sequence

The DNA part of each control module can be divided into three main regions, the core or basal promoter elements, the promoter proximal elements and the distal enhancer elements (Figure 9.1). The best characterized core promoter element is the TATA box, a DNA sequence that is rich in A-T base pairs and located 25 base pairs upstream of the transcription start site. The TATA box is recognized by one of the basal transcription factors, the TATA box-binding protein, TBP, which is part of a multisubunit complex called TFIID. This complex in combination with RNA polymerase 11 and other basal transcription factors such as TFIIA and TFIIB form a preinitiation complex for transcription. 

DNA-dependent synthesis of RNA in E. coli is catalyzed by one enzyme, consisting of five polypeptide subunits. The complete holoenzyme is composed of four polypeptides (the core enzyme) and an additional polypeptide that confers specificity for initiation at promoter sequences in the DNA template. 

A simplified diagram of transcription is shown here. Double-stranded DNA (dsDNA) is shown as a long rectangle. RNA polymerase binds to a region of DNA called a core promoter The core promoter consists of all the DNA between the TATA sequence and the transcription start site. The core promoter is a short stretch of DNA that serves to bind and orient RNA polymerase, and the basal transcription factors. The TATA sequence, which is composed of only four nucleotides T A, T, and A), usually occurs about 25 base pairs upstream of the transcription start site. The TATA-binding protein is a special protein that binds to the TATA sequence prior to initiating transcription. 

A striking pattern is evident when the sequences of many prokaryotic promoters are compared. Two common motifs are present on the 5 (upstream) side of the transcription start site. They are known as the —10 sequence and the —35 sequence because they are centered at about 10 and 35 nucleotides upstream of the start site. The region containing these sequences, which spans as many as 40 nucleotides upstream from the start site, is called the core promoter. The —10 and —35 sequences are each 6 bp long. Their consensus (average) sequences, deduced from analyses of many promoters (Figure 29.4), are... 

Outside the core promoter in a subset of highly expressed genes is the upstream element (also called the UP element for upstream element). This sequence is present from 40 to 60 nucleotides upstream of the transcription start site. The UP element is bound by the ol subunit of RNA polymerase and serves to increase the efficiency of transcription by creating an additional binding site for the polymerase. 

Promoters are DNA regions capable of specific initiation of transcription (start of RNA synthesis) and consist of three basic regions (See Figure 4.2). The part determining the exact nucleotide for transcriptional initiation is called the core promoter and is the stretch of DNA sequence where the RNA polymerase and its cofactors assemble on the promoter. 

Michael Zhang [58] published a new method to detect TATA-box containing core promoters by discrimination analysis. This method is available via a WWW-interface, which already requires restriction of the sequence length to 1 kb. Core Promoter Search and NNPP are alternative implementations of a similar general promoter model and can be applied in parallel. 

It is worth considering which motiflists will be used in a search. For example, using motifs from low complexity clusters (i.e., where the consensus is coming from close relative species like primates) will result in search of almost the entire promoter region, not only the conserved motifs. It is also meaningless to use motifs of the 1000 or 3000 bp promoter sequences, if the query is a core promoter element. 

Pol II promoters have four elements (Figure 11.18). The first includes a variety of upstream elements, which act as enhancers and silencers. Specific binding proteins either activate transcription above basal levels, in the case of enhancers, or suppress it, in the case of silencers. Two common elements that are close to the core promoter are the GC box (-40), which has a consensus sequence of GGGGGG, and the GAAT box (extending to -110), which has a consensus sequence of GGGGAATGT. 

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