Programmable Sequence-Specific Transcriptional Regulation of Mammalian Genome Using Designer TAL Effectors

The ability to direct functional domains to specific DNA sequences is a long sought-after goal for studying and engineering biological processes. Transcription activator like effectors (TALEs) from Xanthomonas sp. present a promising platform for designing sequence-specific DNA binding proteins. Her...

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Detalles Bibliográficos
Autores principales: Zhang, Feng, Cong, Le, Lodato, Simona, Kosuri, Sriram, Church, George, Arlotta, Paola
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084533/
https://www.ncbi.nlm.nih.gov/pubmed/21248753
http://dx.doi.org/10.1038/nbt.1775
Descripción
Sumario:The ability to direct functional domains to specific DNA sequences is a long sought-after goal for studying and engineering biological processes. Transcription activator like effectors (TALEs) from Xanthomonas sp. present a promising platform for designing sequence-specific DNA binding proteins. Here we describe a robust and rapid method for overcoming the difficulty of constructing TALE repeat domains. We synthesized 17 designer TALEs (dTALEs) that are customized to recognize specific DNA binding sites, and demonstrate that dTALEs can specifically modulate transcription of endogenous genes (Sox2 and Klf4) from the native genome in human cells. dTALEs provide a designable DNA targeting platform for the interrogation and engineering of biological systems.

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