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Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains

2012; Nature Portfolio; Volume: 3; Issue: 1 Linguagem: Inglês

10.1038/ncomms1962

2041-1723

Le Cong, Ruhong Zhou, Yu-chi Kuo, Margaret M Cunniff, Feng Zhang,

RNA Interference and Gene Delivery

Transcription activator-like effectors are sequence-specific DNA-binding proteins that harbour modular, repetitive DNA-binding domains. Transcription activator-like effectors have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the transcription activator-like effector toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat-variable diresidue Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective transcription activator-like effector transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using transcription activator-like effectors.