Artigo Acesso aberto Revisado por pares

Robust, synergistic regulation of human gene expression using TALE activators

2013; Nature Portfolio; Volume: 10; Issue: 3 Linguagem: Inglês

10.1038/nmeth.2366

ISSN

1548-7105

Autores

Morgan L. Maeder, Samantha J Linder, Deepak Reyon, James Angstman, Yanfang Fu, Jeffry D. Sander, J. Keith Joung,

Tópico(s)

RNA Interference and Gene Delivery

Resumo

TAL effector (TALE)–based transcription factors robustly induce transcription when targeted to DNase I hypersensitive sites in a gene promoter in human cells, even more so when several TALE transcription factors work in synergy at the same promoter. Tunable expression of endogenous genes will be of great interest in basic research and in synthetic biology. Artificial activators designed using transcription activator–like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

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