A DNA-Binding Protein Factor Recognizes Two Binding Domains within the Octopine Synthase Enhancer Element

1990 ◽  
Vol 2 (3) ◽  
pp. 215
Author(s):  
James G. Tokuhisa ◽  
Karambir Singh ◽  
Elizabeth S. Dennis ◽  
W. James Peacock
Keyword(s):  
Dna Binding ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Enhancer Element ◽  
Binding Domains ◽  
Protein Factor

scholarly journals Rhodopsin targeted transcriptional silencing by DNA-binding

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Salvatore Botta ◽  
Elena Marrocco ◽  
Nicola de Prisco ◽  
Fabiola Curion ◽  
Mario Renda ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Repression ◽  
Binding Protein ◽  
Regulatory Element ◽  
Transcriptional Silencing ◽  
Dna Binding Protein ◽  
Gain Of Function ◽  
Dna Binding Domains ◽  
Binding Domains

Transcription factors (TFs) operate by the combined activity of their DNA-binding domains (DBDs) and effector domains (EDs) enabling the coordination of gene expression on a genomic scale. Here we show that in vivo delivery of an engineered DNA-binding protein uncoupled from the repressor domain can produce efficient and gene-specific transcriptional silencing. To interfere with RHODOPSIN (RHO) gain-of-function mutations we engineered the ZF6-DNA-binding protein (ZF6-DB) that targets 20 base pairs (bp) of a RHOcis-regulatory element (CRE) and demonstrate Rho specific transcriptional silencing upon adeno-associated viral (AAV) vector-mediated expression in photoreceptors. The data show that the 20 bp-long genomic DNA sequence is necessary for RHO expression and that photoreceptor delivery of the corresponding cognate synthetic trans-acting factor ZF6-DB without the intrinsic transcriptional repression properties of the canonical ED blocks Rho expression with negligible genome-wide transcript perturbations. The data support DNA-binding-mediated silencing as a novel mode to treat gain-of-function mutations.

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