Zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
finger transcription factors or ZF-TFs, are
transcription factors composed of a
zinc finger-
binding domain
In molecular biology, binding domain is a protein domain which binds to a specific atom or molecule, such as calcium or DNA. A protein domain is a part of a protein sequence and a tertiary structure that can change or evolve, function, and live ...
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.
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.
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.
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.
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
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
overexpression in human
adenocarcinomas)
and anti-retrovirals (e.g. HIV-1
).
See also
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Artificial transcription factor
Artificial transcription factors (ATFs) are engineered individual or multi molecule transcription factors that either activate or repress gene transcription (biology).
ATFs often contain two main components linked together, a DNA-binding domain an ...
, of which the ZF-TF is a type
*
Gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
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Zinc finger proteins
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Zinc finger chimera
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Zinc finger nuclease
Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enables zinc ...
References
{{HIVpharm
Transcription factors
Zinc proteins