Regulatory sequences

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.

Activation of transcription by the binding of a transcription factor to a DNA-regulatory sequence. 

It is now conventional to consider that a gene includes regulatory sequences as well as the region that... 

Fig. 2. Analysis of Aspergillus niger pectate lyase promoters for putative regulatory sequences...

Shen, J., and Hirsh, J. (1994). Cis-regulatory sequences responsible for alternative splicing of the Drosophila dopa decarboxylase gene. Mol. Cell. Biol. 14, 7385-7393. 

Hirsh, J., Morgan, B. A and Scholnick, S. (1986). Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene. Mol. Cell. Biol. 6 4548-4557. 

Figure 4. Transcriptional regulatory sequences of the mouse c-mos gene. Transcription in oocytes and spermatocytes initiates 53 and approximately 280 base pairs upstream of the c-mos ATG, respectively. Efficient transcription in oocytes requires an initiator (Inr)-I ike sequence located downstream of the transcription start site. A negative regulatory element (NRE) located upstream of the spermatocyte promoter acts to suppress c-mos transcription in somatic cells.

Pennacchio LA, Rubin EM. Genomic strategies to identify mammalian regulatory sequences. Nature Rev Genet 2001 2 100-109. 

Hentze, M. W., Gebauer, F., and Preiss, T. (2006). Cis-regulatory sequences and transacting factors in translational control. In Translational Control in Biology and Medicine (M. B. Mathews, et al., eds.), pp. 273—299. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 

Intravesical infusion of linear PEI/pDNA polyplexes was evaluated in patients with superficial bladder cancer where intravesical therapy with bacillus Calmette-Guerin had failed [6, 224]. Patients had low grade superficial bladder cancer, which expressed H19. The therapeutic pDNA contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. Escalating doses of 2-20 mg plasmid per intravesical treatment were applied, with responders continuing to receive polyplexes once a month every month for 1 year. The treatment resulted in complete ablation of the marker tumor, without any new tumors in four of the 18 patients (22% overall complete response rate). Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. 

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