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Nat Commun DOI:10.1038/ncomms1962

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

Publication TypeJournal Article
Year of Publication2012
AuthorsCong, L, Zhou, R, Kuo, Y-C, Cunniff, M, Zhang, F
JournalNat Commun
Date Published2012 Jul 24
KeywordsCell Line, Computational Biology, DNA, DNA-Binding Proteins, Genetic Engineering, Humans, Models, Molecular, Transcription Factors, Transcriptional Activation

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.


Alternate JournalNat Commun
PubMed ID22828628
PubMed Central IDPMC3556390
Grant ListDP1 MH100706 / MH / NIMH NIH HHS / United States
R01 NS073124 / NS / NINDS NIH HHS / United States
1R01NS073124 / NS / NINDS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States