Zinc finger protein transcription factor

Zinc finger protein transcription factors or ZFP-TFs, consisting of activators and repressors are transcription factors composed of a zinc finger protein domain (ZFP) and any of a variety of transcription-factor effector-domains which exert their modulatory effect in the vicinity of any sequence to which the ZFP domain binds.^[1]

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Zinc finger protein transcription factors can be encoded by genes small enough to fit a number of such genes into a single vector, allowing the medical intervention and control of expression of multiple genes and the initiation of an elaborate cascade of events. In this respect, it is also possible to target a sequence which is common to multiple (usually functionally related) genes in order to control the transcription of all these genes with a single transcription factor. Alternatively, it is possible to target a family of related genes by targeting and modulating the expression of the endogenous transcription factor(s) which control(s) them. They also have the advantage that the targeted sequence need not be symmetrical unlike with most other DNA-binding motifs based on natural transcription factors which bind as dimers.^[1]

Applications

By targeting the ZFP towards a specific DNA sequence and attaching the necessary effector domain, it is possible to downregulate or upregulate the expression of the gene(s) in question while using the same DNA-binding domain. The expression of a gene can also be downregulated by blocking elongation by RNA polymerase (without the need for an effector domain) in the coding region or alternatively, RNA itself can also be targeted.^[2][1] Besides the obvious development of tools for the research of gene function, engineered ZFP-TFs have enormous therapeutic potential including correction of abnormal gene expression profiles (e.g. erbB-2 overexpression in human adenocarcinomas^[3][4] and anti-retrovirals (e.g. HIV-1^[5]).

References

1. ^ ^{a b c} Gommans WM, Haisma HJ, Rots MG (2005). "Engineering zinc finger protein transcription factors: the therapeutic relevance of switching endogenous gene expression on or off at command". J. Mol. Biol. 354 (3): 507–19. doi:10.1016/j.jmb.2005.06.082. PMID 16253273.
2. ^ Wu H, Yang WP, Barbas CF (1995). "Building zinc fingers by selection: toward a therapeutic application". Proc. Natl. Acad. Sci. U.S.A. 92 (2): 344–8. PMID 7831288.
3. ^ Beerli RR, Dreier B, Barbas CF (2000). "Positive and negative regulation of endogenous genes by designed transcription factors". Proc. Natl. Acad. Sci. U.S.A. 97 (4): 1495–500. doi:10.1073/pnas.040552697. PMID 10660690.
4. ^ Beerli RR, Segal DJ, Dreier B, Barbas CF (1998). "Toward controlling gene expression at will: specific regulation of the erbB-2/HER-2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks". Proc. Natl. Acad. Sci. U.S.A. 95 (25): 14628–33. PMID 9843940.
5. ^ Segal DJ, Gonçalves J, Eberhardy S, et al (2004). "Attenuation of HIV-1 replication in primary human cells with a designed zinc finger transcription factor". J. Biol. Chem. 279 (15): 14509–19. doi:10.1074/jbc.M400349200. PMID 14734553.

See also

• Zinc finger chimera
• Zinc finger protein
• Zinc finger nuclease
• Gene therapy