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| Content Provider | PubMed Central |
|---|---|
| Author | Botta, Salvatore Marrocco, Elena Prisco, Nicola De Curion, Fabiola Renda, Mario Sofia, Martina Lupo, Mariangela Carissimo, Annamaria Bacci, Maria Laura Gesualdo, Carlo Rossi, Settimio Simonelli, Francesca Surace, Enrico Maria |
| Editor | Nathans, Jeremy |
| Copyright Year | 2016 |
| Abstract | 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. |
| Related Links | http://dx.doi.org/10.7554/eLife.12242 |
| Starting Page | 12242 |
| File Format | |
| ISSN | 2050084X |
| e-ISSN | 2050084X |
| Journal | eLife |
| Volume Number | 5 |
| Language | English |
| Publisher | eLife Sciences Publications, Ltd |
| Publisher Date | 2016-03-14 |
| Access Restriction | Open |
| Rights Holder | eLife Sciences Publications, Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology |
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