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Biotechnology

Putting a finger on gene expression

Nature Reviews Drug Discovery volume 2, pages 6–7 (2003)Cite this article

Natural transcription factors usually contain two domains: an effector domain, which interacts with other components of the transcriptional machinery to up- or down-regulate gene expression, and a DNA-binding domain, which targets the transcription factor to specific sites on chromosomal DNA. Zinc-finger domains are commonly used for DNA binding by natural transcription factors, and greater understanding of how these domains recognize specific DNA sequences now allows the design of ZFP-based transcription factors that will bind specifically to selected target sequences.

Rebar et al. designed ZFP-based transcription factors — which contained a zinc-finger domain fused to an activating effector domain — to target DNA sites around the mouse gene encoding vascular endothelial growth factor A (Vegfa) that were predicted to lead to a strong influence on gene transcription. Viral vectors were then used to express the ZFP-based transcription factors in the ears of mice, which resulted in new blood vessel growth due to an increase in expression of Vegfa. Further experiments showed that such ZFP-based transcription factors could accelerate wound healing in a mouse model.

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References

ORIGINAL RESEARCH PAPER

  1. Rebar, E. J. et al. Induction of angiogenesis in a mouse model using engineered transcription factors. Nature Med. 8, 1427–1432 (2002)

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FURTHER READING

  1. Pabo, C. O., Peisach, E. & Grant, R. A. Design and selection of novel Cys2His2 zinc finger proteins. Annu. Rev. Biochem. 70, 313–340 (2002)

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Authors
  1. Peter Kirkpatrick
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Kirkpatrick, P. Putting a finger on gene expression. Nat Rev Drug Discov 2, 6–7 (2003). https://doi.org/10.1038/nrd994

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