Promoter upstream elements

Ellis, J.G., Llewellyn, D.J., Dennis, E.S. Peacock, W.J. (1987). Maize Adh-1 promoter sequences control anaerobic regulation addition of upstream promoter elements from constitutive genes is necessary for expression in tobacco. EM BO Journal, 6, 11-16. 

A third class of sequence elements can either increase or decrease the rate of transcription initiation of eukaryotic genes. These elements are called either enhancers or repressors (or silencers), depending on which effect they have. They have been found in a variety of locations both upstream and downstream of the transcription start site and even within the transcribed portions of some genes. In contrast to proximal and upstream promoter elements, enhancers and silencers can exert their effects when located hundreds or even thousands of bases away from transcription units located on the same chromosome. Surprisingly, enhancers and silencers can function in an orientation-independent fashion. Literally hundreds of these elements have been described. In some cases, the sequence requirements for binding are rigidly constrained in others, considerable sequence variation is... 

Activator proteins (and a few repressors) are important in eukaryotes, as they are in prokaryotes. The DNA sequences to which activator proteins bind in eiikaryotic DNA are called response elements. A few response elements are located within the promoter region (upstream promoter elements [UPE]), but most are outside the promoter and often clustered to form an enhancer region that allows control of gene expression by multiple signals (Figure 1-5-4). 

Only the proximity of the upstream promoter element to the -25 sequence distinguishes it from an enhancer. Upstream promoter elements include ... 

Upstream promoter elements (general transcription factors)... 

FIGURE 28-2 Consensus sequence for many E. coli promoters. Most base substitutions in the -10 and —35 regions have a negative effect on promoter function. Some promoters also include the UP (upstream promoter) element (see Fig. 26-5). By convention, DNA sequences... 

However, it is now clear that some upstream promoter elements and enhancers show strong similarities physically and functionally so that the distinction is not as clear as was once thought. For enhancers located a long distance away from the gene being controlled, interaction between transcription factors bound to the enhancer and to promoter elements near the gene occurs by looping out of the DNA between the two sets of elements (Fig. 2). 

Fig. 1. A model for the mechanism whereby steroid hormones regulate rates of gene transcription. Steroids (S) bind with receptors (R) to form a steroid-receptor complex that interacts with DNA sequences called hormone response elements (HRE). These HREs are at variable distances from the gene promoter which frequently consists of upstream promoter elements (UPE) and conserved elements such as TATA box (TATA).

Figure 29.17 Common eukaryotic promoter elements. Each eukaryotic RNA polymerase recognizes a set of promoier elements—sequences in DNA that promote transcription 1 he KNA polymerase I promoter consists of a ribosomal initator (rlnr) and an upstream promoter element (UPE). Tfie RNA polymerase II promotei likewise includes an initator element (Inr) and may also include either a TATA box or a downstream promoter dement (DPE), Separate from the promoter region, enhancer dements bind specific transcription factors. RNA polymerase III promoters consist of conserved sequences that lie within the transcribed genes.

A detailed functional analysis of the immunoglobulin promoter elements is not available. However, comparison of sequences from a number of immunoglobulin promoters revealed the presence of a well-conserved octanucleotide consensus (ATGCAAAT) in all VH promoters and its complement (ATTTGCAT) in all VL promoters as well as in the heavy chain enhancer [54,55], This octanucleotide has been shown to be essential for transcription in both VH and VK promoters, as deletion of it abolishes promoter activity [46,55,56]. Furthermore, in the presence of the IgH enhancer, the octanucleotide is a sufficient VH upstream promoter element as measured in transfection assays [57],... 

Pelham HRB (1982) A regulatory upstream promoter element in the Drosophila hsp70 heat shock gene. Cell 30 517-528... 

CRP (cAMP receptor protein), and for the upstream promoter elements (4,17). The N-terminal region (up to residue 235) is involved in the assembly of the active enzyme molecule. 

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. 

Chou WY, Stewart MJ, Kruijer W, Crabb DW. The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors. Arch Biochem Biophys 2000 280 192-200. 

Chen Z, Zheng H, Dong KW (2001) Identification of negative and positive estrogen response elements in human GnRH upstream promoter in the placental JEG-3 cells. Mol Cell Endocrinol 184 125-134... 

The holoenzyme binds to a promoter region about 40-60 bp in size and then initiates transcription a short distance downstream (i.e. 3 to the promoter). Within the promoter lie two 6-bp sequences that are particularly important for promoter function and which are therefore highly conserved between species. Using the convention of calling the first nucleotide of a transcribed sequence as +1, these two promoter elements lie at positions -10 and -35, that is about 10 and 35 bp, respectively, upstream of where transcription will begin (Fig. 1). 

Most promoter sites for RNA polymerase II include a highly conserved sequence located about 25-35 bp upstream (i.e. to the 5 side) of the start site which has the consensus TATA(A/T)A(A/T) and is called the TATA box (Fig. 2). Since the start site is denoted as position +1, the TATA box position is said to be located at about position -25. The TATA box sequence resembles the -10 sequence (see Topic G2) in prokaryotes (TATAAT) except that it is located further upstream. Both elements have essentially the same function, namely recognition by the RNA polymerase in order to position the enzyme... 

The rRNA promoter consists of a core element which straddles the transcriptional start site (designated as position +1) from residues -31 to +6 plus an upstream control element (UCE) about 50-80 bp in size and located about 100 bp upstream from the start site (i.e. at position -100 Fig. 4b). A transcription factor called upstream binding factor (UBF) binds both to the UCE as well as to a region next to and overlapping with the core element. Interestingly, TATA box binding protein (TBP see Topic G6), also binds to the rRNA promoter (in fact, TBP is required for initiation by all three eukaryotic RNA polymerases). The UBF and TBP transcription factors interact with each other and with RNA Pol I to form a transcription initiation complex. The RNA Pol I then transcribes... 

Archaebacterial RNA polymerases are very different from their eubacterial counterparts and more closely resemble eukaryotic enzymes both in their subunit complexity and in their amino acid sequences (for review, see Puehler et al., 1989). This view is also reflected in the diversity of the DNA sequences that are used by the transcription apparatus as signals for initiation of transcription, namely, the promoters. Many attempts were made to identify a consensus promoter structure (Zillig et al., 1988). However, as more genes are isolated and characterized, the picture becomes less coherent. Earlier identification of two upstream sequences, box A and box B, located around positions — 30 and + 1, respectively, gave way to two elements —DPE (distal promoter element) and PPE (proximal promoter element)—located - 38 to - 25 and — 11 to — 2, respectively (Reiter et al., 1990). The DPE encompasses the box A sequence TTTA(A or T)A, but the PPE sequence seems to depend more on an (A + T)-rich sequence rather than on a specific DNA sequence. 

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