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'''Zinc finger protein transcription factors''' or ZFP-TFs, consisting of activators and repressors are [[transcription factors]] composed of a [[zinc finger protein]] domain and any of a variety of transcription-factor effector-domains which exert their modulatory effect around any sequence to which the ZFP domain binds |
'''Zinc finger protein transcription factors''' or ''ZFP-TFs'', consisting of activators and repressors are [[transcription factors]] composed of a [[zinc finger protein]] domain and any of a variety of transcription-factor effector-domains which exert their modulatory effect around any sequence to which the ZFP domain binds. <ref name="gommans2005">{{cite journal |author=Gommans WM, Haisma HJ, Rots MG |title=Engineering zinc finger protein transcription factors: the therapeutic relevance of switching endogenous gene expression on or off at command |journal=J. Mol. Biol. |volume=354 |issue=3 |pages=507–19 |year=2005 |pmid=16253273 |doi=10.1016/j.jmb.2005.06.082 |url=http://linkinghub.elsevier.com/retrieve/pii/S0022-2836(05)01143-5}}</ref> |
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Zinc finger protein transcription factors (ZFP-TFs) can be encoded by genes small enough to fit a number of such genes into a single [[Viral vector|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 common sequence to control the transcription of multiple related genes with a single transcription factor. Alternatively, it is possible to target a family of related genes by targeting 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 |
Zinc finger protein transcription factors (ZFP-TFs) can be encoded by genes small enough to fit a number of such genes into a single [[Viral vector|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 common sequence to control the transcription of multiple related genes with a single transcription factor. Alternatively, it is possible to target a family of related genes by targeting 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 <ref name="gommans2005"/>. |
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== Applications == |
== Applications == |
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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, using the same DNA-binding domain. The expression of a gene can also be downregulated by blocking RNA polymerase elongation (without an effector domain) in the coding region or RNA itself can be targeted |
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, using the same DNA-binding domain. The expression of a gene can also be downregulated by blocking RNA polymerase elongation (without an effector domain) in the coding region or RNA itself can be targeted. <ref name="wu1995">{{cite journal |author=Wu H, Yang WP, Barbas CF |title=Building zinc fingers by selection: toward a therapeutic application |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue=2 |pages=344–8 |year=1995 |pmid=7831288 |doi= |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=7831288}}</ref><ref name="gommans2005"/> 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 <ref name="beerli2000">{{cite journal |author=Beerli RR, Dreier B, Barbas CF |title=Positive and negative regulation of endogenous genes by designed transcription factors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue=4 |pages=1495–500 |year=2000 |pmid=10660690 |doi=10.1073/pnas.040552697 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10660690}}</ref><ref name="beerli1998">{{cite journal |author=Beerli RR, Segal DJ, Dreier B, Barbas CF |title=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 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=25 |pages=14628–33 |year=1998 |pmid=9843940 |doi= |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9843940}}</ref> and anti-retrovirals (e.g. HIV-1 {{cite journal |author=Segal DJ, Gonçalves J, Eberhardy S, ''et al'' |title=Attenuation of HIV-1 replication in primary human cells with a designed zinc finger transcription factor |journal=J. Biol. Chem. |volume=279 |issue=15 |pages=14509–19 |year=2004 |pmid=14734553 |doi=10.1074/jbc.M400349200 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=14734553}}). |
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== References == |
== References == |
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</references> |
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Beerli, R. R., B. Dreier and C. F. Barbas, 3rd (2000). "Positive and negative regulation of endogenous genes by designed transcription factors." Proceedings of the National Academy of Sciences USA 97(4): 1495-500. |
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Beerli, R. R., D. J. Segal, B. Dreier and C. F. Barbas, 3rd (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." Proceedings of the National Academy of Sciences USA 95(25): 14628-33. |
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Gommans, W. M., H. J. Haisma and M. G. Rots (2005). "Engineering zinc finger protein transcription factors: the therapeutic relevance of switching endogenous gene expression on or off at command." Journal of Molecular Biology 354(3): 507-19. |
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Segal, D. J., J. Goncalves, S. Eberhardy, C. H. Swan, B. E. Torbett, X. Li and C. F. Barbas, 3rd (2004). "Attenuation of HIV-1 replication in primary human cells with a designed zinc finger transcription factor." Journal of Biological Chemistry 279(15): 14509-19. |
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Wu, H., W. P. Yang and C. F. Barbas, 3rd (1995). "Building zinc fingers by selection: toward a therapeutic application." Proceedings of the National Academy of Sciences USA 92(2): 344-8. |
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== See also == |
== See also == |
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Revision as of 01:07, 11 December 2007
Zinc finger protein transcription factors or ZFP-TFs, consisting of activators and repressors are transcription factors composed of a zinc finger protein domain and any of a variety of transcription-factor effector-domains which exert their modulatory effect around any sequence to which the ZFP domain binds. [1]
Zinc finger protein transcription factors (ZFP-TFs) 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 common sequence to control the transcription of multiple related genes with a single transcription factor. Alternatively, it is possible to target a family of related genes by targeting 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, using the same DNA-binding domain. The expression of a gene can also be downregulated by blocking RNA polymerase elongation (without an effector domain) in the coding region or RNA itself can 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 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)).
References
</references>
See also
Zinc finger chimera Zinc finger protein Zinc finger nuclease Gene therapy
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link)