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HERO ID
1508079
Reference Type
Journal Article
Title
Benzoate X receptor zinc-finger gene switches for drug-inducible regulation of transcription
Author(s)
Schwimmer, LJ; Gonzalez, B; Barbas, CF
Year
2012
Is Peer Reviewed?
1
Journal
Gene Therapy
ISSN:
0969-7128
EISSN:
1476-5462
Volume
19
Issue
4
Page Numbers
458-462
Language
English
PMID
21796215
DOI
10.1038/gt.2011.112
Web of Science Id
WOS:000302769800014
Abstract
Targeted zinc-finger (ZF) DNA-binding domains in conjunction with nuclear receptor ligand-binding domains (LBDs) produce chemically inducible gene switches that have applications in gene therapy and proteomic and genomic research. The benzoate X receptor-β (BXRβ) LBD was used to construct homodimer and single-chain ZF transcription factors (ZF(TF)s). These ZF(TF)s specifically regulated the transcription of target genes in response to two ligands, ethyl-4-hydroxybenzoate and propyl-4-hydroxybenzoate, in a dose-dependent manner. The ZF(TF)s also regulated the expression of endogenous intercellular adhesion molecule-1 in response to either ligand. The advantage of BXRβ-based ZF(TF)s is that the ligands are inexpensive and easily synthetically modified, making the system a base for creation of orthogonal ligand-receptor pairs and expanding the gene-switch toolbox.
Keywords
gene switch; zinc finger; transcription factor; benzoate X receptor; nuclear receptor
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