Enhancer elements, distal

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. 

Figure 9.1 The transcriptional elements of a eucaryotic structural gene extend over a large region of DNA. The regulatory sequences can be divided into three main regions (1) the basal promoter elements such as the TATA box, (2) the promoter proximal elements close to the initiation site, and (3) distal enhancer elements far from the initiation site.

The regulation of transcription can simply be viewed as correctly localizing RNA polymerase to the appropriate position to initiate transcription. From this vantage, the function of promoters (elements located proximal to the transcription start site) and enhancers (elements located more distal to the transcription start site) are essentially the same in that they recruit in a cooperative fashion and localize RNA polymerase to its initiation site. In the absence of these elements, the binding of RNA polymerase to DNA is both of low-affinity and promiscuous. Another function proposed for enhancers is to relieve chromatin-mediated repression of a weak promoter (Majumder and DePamphilis, 1995). It should be noted that these two functions are not mutually exclusive. 

The distal enhancer also contains five sequence elements that are conserved between D. melanogaster and D. virilis (Johnson et al., 1989 Lundell and Hirsh, 1992) (Fig. 5). Both tissue-specific and cell-specific regulatory functions have been attributed to these elements. Here we will... 

The second cell-specific regulatory element within the distal enhancer is named SER. Loss of this element, which is at the extreme distal edge of the enhancer, leads to a selective loss of DDC expression in the ventral lateral serotonin cells (Johnson et al., 1989 Lundell and Hirsh, 1992) (Fig. 6C). This element has been delimited to about 40 bp and shows unexpected complexity, consisting of two functionally redundant elements. These two subelements, SERl and SERr, are each sufficient to allow normal DDC expression in the ventral lateral serotonin neurons if the other is deleted. In spite of this functional similarity, no sequence similarity is apparent between the two regions. The region of conservation between D. melanogaster and D. virilis is limited to SERl. 

Promoter region containing proximal and distal elements and enhancers... 

Enhancer-dependent expression is observed following transplantation of an injected pronucleus into a two-cell blastomere (Henery et al., 1995) (Figure 4). The first mitosis—and concomitant loss of the plasmid from the injected pronucleus—was circumvented by the transplantation procedure and hence cannot account for the enhancer requirement observed in the two-cell embryo. The luciferase reporter gene is driven by the / promoter, which has two Spl binding sites (termed the proximal and distal sites)—a CAAT box binding site that binds CTF and a TATA box that binds TBP. Analysis of the expression of a set of linker scanning mutations that inactivated each of these sites without altering the distances between each of the promoter elements revealed that each mutation had the same relative effect on tk... 

What is the difference between a promoter-proximal element and a distal enhancer ... 

In addition to the proximal promoter, distal enhancer-like elements have been identified in organisms such as mouse, Drosophila, and Xenopus (Reeder, 1984). These sequences consist of multiple repeats of either 61 or 81 bp in length and function in either orientation, either upstream or downstream of the promoter. In Xenopus, these repeated sequences share regions of homology with the rDNA promoter and can compete for basal... 

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