Tissue-specific promoters

Wippersteg, V., Sajid, M., Walshe, D., Khiem, D., Salter, J.P., McKerrow, J.H., Grevelding, C.G. and Caffrey, C.R. (2005) Biolistic transformation of Schistosoma mansoni with 5 flanking regions of two peptidase genes promotes tissue-specific expression. International journal for Parasitology 35, 583-589. 

Tissue-specific regulation of gene exptession can be provided by control elements in the promoter or by the... 

Figure 37-14. Alternative promoter use in the liver and pancreatic B cell glucokinase genes. Differential regulation of the glucokinase GK) gene is accomplished by the use of tissue-specific promoters. The B cell GK gene promoter and exon 1B are located about 30 kbp upstream from the liver promoter and exon 1L. Each promoter has a unique structure and is regulated differently. Exons 2-10 are identical in the two genes, and the GK proteins encoded by the liver and B cell mRNAs have identical kinetic properties.

In Drosophila the two tissue-specific mRNAs are generated by alternative splicing of a single primary transcript (Fig. 9). In vertebrates the two tissue specific AADC transcripts are generated from two alternative promoters (Fig. 11) (Albert et al., 1992 Ichinose et al., 1992 Thai et al., 1993). In neural tissue transcription initiates from exon Nl, whereas in non-neural tissue transcription initiates from exon LI. This produces two distinct primary transcripts that are then spliced from the first exon (LI or Nl) to exon 2 to generate two tissue-specific mRNAs. Translation initiates within exon 2, such that the same AADC protein product is synthesized from both AADC mRNAs. 

The highly restricted tissue-specific transcription of c-mos poses an interesting problem in gene regulation during germ cell development. Moreover, c-mos is transcribed from different promoters in mouse spermatocytes and oocytes (Fig. 4) (Propst et al., 1987). In spermatocytes, transcription initiates approximately 280 nucleotides upstream of the c-mos ATG (Propst et al., 1987), whereas the transcription start site in oocytes has been mapped to 53 base pairs upstream of the ATG (Pal et al., 1991). Neither the spermatocyte nor oocyte promoter regions are... 

Ponnazhagan and Kwon (1992) reported a putative tissue-specific ds-element (TE-1) located at-236 bp of the mouse tyrosinase promoter. They partially purified a TE-1 binding protein (approximately 49 kDa in size), but tissue specificity remains to be confirmed by a more detailed analysis. For the human tyrosinase promoter, Shibata et al. (1992) identified a 200-bp pigment cell-specific enhancer, located between -2.0 and -1.8 kb. A minimum core sequence of 39 bp was shown to be sufficient to confer the specific activity, although other regions (not identified so far) within the 200-bp fragment are required for more efficient expression in melanoma cells (Shibata et al., 1992). 

More recently, various modifications have been introduced to this basic retroviral system. The inclusion of the 5 end of the gag gene is shown to enhance levels of vector production by up to 200-fold. Additionally, specific promoters have been introduced in order to attempt to control expression of the inserted gene. Most work has focused upon the use of tissue-specific promoters in an effort to limit expression of the desired gene to a specific tissue type. 

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