Not only that, but the sequence of each core promoter motif (i.e. TATA-Box) is variable to some degree. That said, nearly half of human promoters lack both a TATA-box and an Inr! The take home message? There are no universal sequence motif required for transcription initiation in Eukaryotes. This DNA motif spans the TSS and also recruits TFIID. The core promoter motif found most often is the Initiator (Inr). For example, 24% of human genes have a TATA-box. We now know it is only present in a small minority. Initially, it was thought to be an essential motif that most core promoters possess. The TATA-box recruits TFIID to the core promoter. One of the first core promoter motif identified was the TATA-box. The Inr spans the TSS (+1) while the TATA-box is upstream and the MTE and DPE motifs are downstream. TATA, Inr, MTE and DPE are DNA sequence motifs positioned along the core promoter as shown. Basal levels of transcription are often modified by transcriptional activators and/or repressors.įigure 5.2: A schematic of a focused core promoter and the GTFs/RNA polymerase II that bind to it. This large, multiprotien complex (called the preinitiation complex or PIC) initiates basal levels of transcription 37. Once TFIID and TFIIB bind a focused core promoter, they recruit and stabilize other GTFs which together recruit and stabilize RNA polymerase II to the TSS. These DNA motifs serve as binding sites for GTFs (namely TFIID and TFIIB). Each includes a set of short, DNA sequences called core promoter motifs 36. In humans, they are about 80 nt in length and flank 35 the TSS, the so-called +1 position of transcription (Figure 5.2). The right image from Carninci et al. 2006 displays TSS seq data for a number of genes that illustrate each type of promoter.įocused core promoters were the first described and are the best characterized (See Griffiths). In other words, promoters cannot be categorized easily and also include promoters of mixed character (i.e. “broad with peak”) (Figure 5.1).įigure 5.1: The left schematic from Vo ngoc et al. 2017 illustrates the three main types of promoters that are found in animals: Focused, Dispersed and Mixed. In reality, TSS-seq data and other genome-wide studies of transcription initiation suggest that these two main types of core promoters are in fact two ends of a continuum. Both terms “sharp peak” and “broad peak” essentially describe the shape of the TSS-seq histogram data (See Chapter 4). This type of promoter is also called a “broad peak” or “wide peak” promoter. A dispersed promoter, by contrast, contains a large number of transcriptional start sites of equal potency that are dispersed over a 50 to 100 nucleotide region. A focused core promoter (also called a “sharp peak” or “narrow peak” promoter) contains a single predominant TSS that is confined to a small number of nucleotides. TSS-seq data indicates that there are two main types of core promoters: focused and dispersed (Danino et al. 2015). Transcription initiation also requires a number of so-called General Transcription Factors or GTFs 34 and a core promoter sequence.Ī core promoter is defined as the minimal DNA sequence that directs initiation of transcription of a gene. But RNA polymerase II on its own cannot recognize a TSS. Transcription begins once RNA pol II binds near a transcriptional start site (TSS) of a gene. Transcription of protein coding genes, like BBS1, require RNA Pol II and will be our focus. There are three RNA polymerases that catalyze transcription in eukaryotes (RNA Pol I, II and III). 9.2 How to Configure the Genome Browser from Scratch.9.1 Create an Account at the UCSC Genome Browser.
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