Cis-elements

A small number of genes lack a TATA box. In such instances, two additional cis elements, an initiator sequence (Inr) and the so-called downstream promoter element (DPE), direct RNA polymerase II to the promoter and in so doing provide basal transcription starting from the correct site. The Inr element spans the start... 

Figure 37-7. Transcription elements and binding factors in the herpes simplex virus thymidine kinase ffW gene. DNA-dependent RNA polymerase II binds to the region of the TATA box (which is bound by transcription factor TEND) to form a multicomponent preinitiation complex capable of initiating transcription at a single nucleotide (+1).The frequency of this event is increased by the presence of upstream c/s-acting elements (the GC and CAAT boxes). These elements bind frans-acting transcription factors, in this example Spl and CTF (also called C/EBP, NF1, NFY). These cis elements can function independently of orientation (arrows).

Dynlacht, B., Attardi, L., Admon, A., Freeman, M., and Tjian, R. (1989). Functional analysis of NTF-1, a developmentally regulated Drosophila transcription factor that binds neuronal cis-elements. Genes Dev. 3 1677-1688. 

R Genes Cis Elements, Trans-factors and Signal Transduction Systems in the Lens, Joram Piatigorksy and Peggy S. Zelen-ka, National Eye Institute, National Institutes of Health, Maryland. Subject Index. 

Hur M-W. Sp3 and Sp4 can repress transcription by competing with Spl for core cis-elements on the human ADH5/FDH minimal promoter. J Biol Chem 1999 274 20-28... 

The a3 isoform is expressed mainly in adult neurons and neonatal cardiomyocytes. The a3 gene exhibits three positively regulating cis elements that bind NP-Y, Spl and Sp2 [10]. Its neuron specificity appears to be related to a neural-restrictive silencer element and a positively acting cis element [11]. 

Mutations that stimulate exon 10 inclusion into the human tau mRNA, which is regulated by an intricate interplay of cis elements and trans factors, cause FTDP-17 and other tauopathies. This suggests that the ratio of exon 10 inclusion to exclusion in the adult brain is one of the factors to determine biological functions of the tau protein. 

Chromatin organization and its relation to function in the intact cell have become part of a broader area of investigation, the organization of the cell nucleus itself. The suceess of modern molecular biology, which has focussed on the characterization of cis-elements in the DNA that affect nuclear events such as... 

Cis-acting DNA elements can he near the start site of transcription or be quite distanced from it. Fmthermore, there are examples among eucaryotes in which the cis element is foimd within the transcribed region. If the cis element is located far from the site of action and its effect is also orientation-independent, then it is termed an enhancer. Fmthermore, one frequently observes in eucaryotes so called composite control regions which contain various cis elements. In this case, several transcription factors act cooperatively in the initiation of transcription. Examples for such cooperative effects are observed among the genes controlled by nuclear receptors. 

DNA-binding proteins can exercise a negative or positive influence on transcription upon binding to their cognate cis element (Fig. 1.20). 

A combination of several cis-elements, and thus several transcriptional activators, are often involved in the regulation of eucaryotic transcription. Transcription activation, in these cases, results from the complex concerted action of various specific DNA-binding proteins. 

Central to the function of the p53 protein is its abUity, as a transcription activator, to specifically bind to corresponding cis elements in the promoter region of various genes and to activate their transcription. The importance of sequence-specific DNA binding for the tumor-suppressing function of p53 became clear when the crystal structure of the complex of p53 protein and a corresponding DNA element were resolved and this structure was compared with the spectrum of known mutations of p53 protein occurring in human tumors (Cho et al., 1994). 

Cis elements involved in transcription in yeast (a) and in vertebrates (b). Upstream activator sequences (UAS) in yeast are similar in function to upstream enhancers in vertebrates. Yeast has no parallel to downstream enhancers found in vertebrates. 

Metz, B.A., Welters, P., Hoffman, H.J., Jensen, E.O., Schell, J. de Bruijn, F.J. (1988). Primary structure and promoter analysis of leghemoglobin gene of the stem nodulated tropical legume Sesbania rostrata conserved coding sequences, cis elements and trans-acting factors. Molecular and General Genetics 214, 181-91. 

Block, A., Dangl, J.L., Hahlbrock, K. Schulze, L.P. (1990). Functional borders, genetic fine structure, and distance rquirements of cis elements mediating light responsiveness of the parsley chalcone synthase promoter. Proceedings of the National Academy of Sciences (USA) 87, 5387-91. 

Kovacs, A.M. and Zimmer, W.E. (1998) Cell specific transcription of the smooth muscle g-actin gene requires both positive and negative acting cis-elements. Gene Exp., 7, 115-129. 

Morishita R, Sugimoto T, Aoki M, et al. In vivo transfection of cis element decoy against nuclear factor factor kB binding sites prevents myocardial infarction. Nat Med 1997 3 894-899. 

Figure 2 Nucleotide sequence of DOR gene 5 flanking region. Sequence is numbered relative to + 1 representing the A nucleotide in the ATG translation start codon, indicated by bold type. Positions of minor transcription initiation sites determined from estimates of RNase protected fragment sizes are indicated with bullets ( ) The two strongest transcription start sites are indicated by asterisks ( ) at positions —142 and —324. The cis elements and corresponding trans factors that have been identified are underlined and labeled above the sequence, respectively. (From Ref. 16.)...

Figure 3 A schematic representation of the cis elements and corresponding trans factors that have been identified in the mouse DOR promoter. The translation start site (ATG) is designated as + 1. The asterisk ( ) marked transcription factor and its cognate binding site are identified in T cells, with the rest in neuronal cells. The (+ ) and (—) indicate positive and negative effects, respectively. EBS stands for Ets-1-binding site.

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