Zinc finger chimera

Zinc finger protein chimera are chimeric proteins composed of a DNA-binding zinc finger protein domain and another domain through which the protein exerts its effect. The effector domain may be a transcriptional activator (A) or repressor (R),[1] a methylation domain (M) or a nuclease (N).[2]

Modification of the endogenous DNA-binding zinc finger domain is the basis of the most advanced field in construction of gene-specific artificial transcription factors.[1] Linking together six ZFPs produces a target-site of 18-19 bp. Assuming specificity to that one sequence and that the sequence of the genome is random, 18 bp is long enough to be unique in all known genomes[3][4] Indeed, the spacing between subsites becomes part of the target sequence due to restrictions in the flexibility of the protein which can be controlled.[1] Targeting sites as small as 9 bp provides some degree of specificity, almost certainly attributable in some part to chromatin occlusion.[4]

  1. ^ 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" (PDF). J. Mol. Biol. 354 (3): 507–19. doi:10.1016/j.jmb.2005.06.082. PMID 16253273.
  2. ^ Durai S, Mani M, Kandavelou K, Wu J, Porteus MH, Chandrasegaran S (2005). "Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells". Nucleic Acids Res. 33 (18): 5978–90. doi:10.1093/nar/gki912. PMC 1270952. PMID 16251401.
  3. ^ Segal DJ, Dreier B, Beerli RR, Barbas CF (1999). "Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences". Proc. Natl. Acad. Sci. U.S.A. 96 (6): 2758–63. Bibcode:1999PNAS...96.2758S. doi:10.1073/pnas.96.6.2758. PMC 15842. PMID 10077584.
  4. ^ a b Dreier B, Fuller RP, Segal DJ, et al. (2005). "Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA sequences and their use in the construction of artificial transcription factors". J. Biol. Chem. 280 (42): 35588–97. doi:10.1074/jbc.M506654200. PMID 16107335.