2006
DOI: 10.1002/mc.20289
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Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein‐2 promoter as a novel anti‐cancer treatment

Abstract: Zinc finger protein transcription factors (ZFP-TFs) are emerging as powerful novel tools for the treatment of many different diseases. ZFPs are DNA-binding motifs and consist of modular zinc finger domains. Each domain can be engineered to recognize a specific DNA triplet, and stitching six domains together results in the recognition of a gene-specific sequence. Inhibition of gene expression can be achieved by fusing a repressor domain to these DNA-binding motifs. In this study, we engineered ZFP-TFs to downre… Show more

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Cited by 26 publications
(20 citation statements)
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References 29 publications
(59 reference statements)
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“…Targeting of the EpCAM promoter by engineered zinc finger protein transcription factors (ZFPs) has already been demonstrated by us. 21 Methyltransferases fused to zinc finger proteins targeting predetermined sites in the DNA to repress gene expression have been reported. 12,22,23 Engineering ZFPs targeted to the EpCAM promoter 21 fused to M.SssI as an effector domain, provides a powerful tool to achieve targeted methylation.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Targeting of the EpCAM promoter by engineered zinc finger protein transcription factors (ZFPs) has already been demonstrated by us. 21 Methyltransferases fused to zinc finger proteins targeting predetermined sites in the DNA to repress gene expression have been reported. 12,22,23 Engineering ZFPs targeted to the EpCAM promoter 21 fused to M.SssI as an effector domain, provides a powerful tool to achieve targeted methylation.…”
Section: Discussionmentioning
confidence: 99%
“…21 Methyltransferases fused to zinc finger proteins targeting predetermined sites in the DNA to repress gene expression have been reported. 12,22,23 Engineering ZFPs targeted to the EpCAM promoter 21 fused to M.SssI as an effector domain, provides a powerful tool to achieve targeted methylation. The ZFP binds specific to the promoter where after the enzyme will methylate only the CpGs close to the ZFP target sequence.…”
Section: Discussionmentioning
confidence: 99%
“…Unlike designer genomic nucleases or RNAi-based approaches, toggle switches can also upregulate silenced gene expression. For example, KRAB and VP64 effector domains were able to downregulate or upregulate the EGP-2 promoter, respectively (21). …”
Section: Introductionmentioning
confidence: 99%
“…MicroRNAs (miRNAs), small interfering RNAs (siRNAs), and peptide motifs such as zinc fingers, play important roles in gene regulation and represent potential therapeutic agents [75,76,77,78]. Nuclease-resistant nucleobase-peptides and nucleobase-proteins comprising both regular peptide segments and polyamide nucleic acid (PNA) [79] segments can be synthesized through the encoded incorporation of NCAAs bearing U(T), C, A, and G nucleobase sidechains.…”
Section: Discussionmentioning
confidence: 99%