Zinc finger transcription factor

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Zinc finger transcription factors or ZF-TFs, are transcription factors composed of a zinc finger-binding domain and any of a variety of transcription-factor effector-domains that exert their modulatory effect in the vicinity of any sequence to which the protein domain binds. [1]

Contents

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 that is common to multiple (usually functionally related) genes in order to control the transcription of all these genes with a single transcription factor. Also, it is possible to target a family of related genes by targeting and modulating the expression of the endogenous transcription factor(s) that 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 that bind as dimers. [1]

Applications

By targeting the ZF-TF toward 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. [2] 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. [1] [3] Besides the obvious development of tools for the research of gene function, engineered ZF-TFs have therapeutic potential including correction of abnormal gene expression profiles (e.g., erbB-2 overexpression in human adenocarcinomas) [4] [5] and anti-retrovirals (e.g. HIV-1 [6] ).

See also

Related Research Articles

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References

  1. 1 2 3 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" (PDF). J. Mol. Biol. 354 (3): 507–19. doi:10.1016/j.jmb.2005.06.082. PMID   16253273.
  2. ↑ Beerli R, Barbas CF (2002). "Engineering polydactyl zinc-finger transcription factors". Nature Biotechnology. 20 (2): 135–141. doi:10.1038/nbt0202-135. PMID   11821858. S2CID   12685879.
  3. ↑ 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. Bibcode:1995PNAS...92..344W. doi: 10.1073/pnas.92.2.344 . PMC   42736 . PMID   7831288.
  4. ↑ 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. Bibcode:2000PNAS...97.1495B. doi: 10.1073/pnas.040552697 . PMC   26462 . PMID   10660690.
  5. ↑ 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. Bibcode:1998PNAS...9514628B. doi: 10.1073/pnas.95.25.14628 . PMC   24500 . PMID   9843940.
  6. ↑ 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.
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