title: Benzoate X receptor zinc-finger gene switches for drug-inducible regulation of transcription.
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.
authors.affiliation: Departments of Molecular Biology and Chemistry, Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Schwimmer
authors.forename: B
authors.initials: B
authors.lastname: Gonzalez
authors.forename: C F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D005786:Gene Expression Regulation; D005821:Genetic Techniques; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D029867:Xenopus Proteins; C112210:benzoate X receptor, Xenopus