Distal enhancer

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 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. 

Sugatani J, Yamakawa K, Tonda E, Nishitani S, Yoshinari K, Degawa M, Abe I, Noguchi H, Miwa M. The induction of human UDP-glucuronosyl-transferase 1A1 mediated through a distal enhancer module by flavonoids and xenobiotics. Biochem Pharmacol 2004 67 989-1000. 

Fig. 10.9 (a) A transcriptional regulator protein bound to a distal enhancer recruits the co-activator CBP and possibiy other co-activators, indicated by... 

Goodwin B, Hodgson E, Liddle C. The orphan human pregnane X receptor mediates the transcription activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 1999 56 1329-39. 

Li, H., Capatanaki, Y. (1994) An E box in the desmin promoter cooperates with the E-box and MEF-2 sites of a distal enhancer to direct muscle-specific transcription. EMBO J 13, 3580-3589. 

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

Wang, H., S. Faucette, T. Sueyoshi, R. Moore, S. Ferguson, M. Negishi et al. (2003). A novel distal enhancer module regulated by PXR/CAR is essential for the maximal induction of CYP2B6 gene expression. J Biol. Chem. 278, 14146-14152. 

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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