Zinc finger transcription factor
{{Short description|Transcription factor}}
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.{{cite journal |vauthors=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://www.rug.nl/farmacie/onderzoek/basiseenheden/therapeuticgenemodulation/publicaties/publicaties2004/2005_6.pdf}}
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 to control the transcription of all these genes with a single transcription factor. Additionally, a group of related genes can be targeted by modulating the expression of the endogenous transcription factor(s) that regulate them. They also have the advantage that the targeted sequence need not be symmetrical unlike most other DNA-binding motifs based on natural transcription factors that bind as dimers.
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.{{cite journal|vauthors=Beerli R, Barbas CF |title=Engineering polydactyl zinc-finger transcription factors|journal=Nature Biotechnology|volume=20|issue=2|pages=135–141|year=2002|doi=10.1038/nbt0202-135|pmid=11821858|s2cid=12685879}} 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 RNA itself can also be targeted.{{cite journal |vauthors=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= 10.1073/pnas.92.2.344|pmc=42736|bibcode=1995PNAS...92..344W |doi-access=free }} In addition to their clear role in advancing gene function research, engineered ZF-TFs also hold therapeutic potential, including the ability to correct abnormal gene expression profiles (e.g., erbB-2 overexpression in human adenocarcinomas){{cite journal |vauthors=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 |pmc=26462|bibcode=2000PNAS...97.1495B |doi-access=free }}{{cite journal |vauthors=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= 10.1073/pnas.95.25.14628|pmc=24500|bibcode=1998PNAS...9514628B |doi-access=free }} and anti-retrovirals (e.g. HIV-1{{cite journal |vauthors=Segal DJ, Gonçalves J, Eberhardy S, etal |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 |doi-access=free }}).
See also
- Artificial transcription factor, of which the ZF-TF is a type
- Gene therapy
- Zinc finger proteins
- Zinc finger chimera
- Zinc finger nuclease
References
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{{Transcription factors and intracellular receptors}}
{{HIVpharm}}