title: Controlling gene expression in Drosophila using engineered zinc finger protein transcription factors.
abstract: Zinc finger protein transcription factors (ZFP TFs) have been designed to control the expression of endogenous genes in a variety of cells. However, thus far the use of engineered ZFP TFs in germline transgenic settings has been restricted to plants. Here we report that ZFP TFs can regulate gene expression in transgenic Drosophila. To demonstrate this, we targeted the promoter of the well-characterized fushi tarazu (ftz) gene with a ZFP TF activator using the VP16 activation domain from Herpes simplex virus, and ZFP TF repressors using the Drosophila methyl-CpG binding domain (MBD)-like Delta protein. Heat-shock-inducible expression of the ZFP TF activator and repressors resulted in reciprocal effects on ftz regulation, as deduced from changes in the staining pattern and intensity of ftz and en gene expression, and from the cuticular analysis of first instar larvae. These data demonstrate the utility of ZFP TFs as tools for controlling gene expression in the context of a metazoan organism.
authors.affiliation: Sangamo BioSciences, Inc., Point Richmond Tech Center, 501, Canal Blvd., Suite A100, Richmond, CA 94804, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Jamieson
authors.forename: Bo
authors.initials: B
authors.lastname: Guan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cradick
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Michael C
authors.initials: MC
authors.lastname: Holmes
authors.forename: Philip D
authors.initials: PD
authors.lastname: Gregory
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Carroll
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019187:Cadmium Compounds; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000138:chemical synthesis / Q000235:genetics* / Q000502:physiology; D051717:Fushi Tarazu Transcription Factors / Q000138:chemical synthesis / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015202:Protein Engineering; D017434:Protein Structure, Tertiary / Q000235:genetics; D013691:Tellurium; D015534:Trans-Activators / Q000138:chemical synthesis / Q000235:genetics* / Q000502:physiology; D016335:Zinc Fingers / Q000235:genetics* / Q000502:physiology
chemical_list: D019187:Cadmium Compounds; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; C115368:MBD2 protein; D015534:Trans-Activators; C497169:ftz protein, Drosophila; D013691:Tellurium; C028337:cadmium telluride