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

Author

Listed:
  • Le Cong

    (Broad Institute of MIT and Harvard
    McGovern Institute for Brain Research, MIT, Massachusetts Institute of Technology
    Program in Biological and Biomedical Sciences, Harvard Medical School)

  • Ruhong Zhou

    (Computational Biology Center, IBM Thomas J. Watson Research Center)

  • Yu-chi Kuo

    (Broad Institute of MIT and Harvard
    McGovern Institute for Brain Research, MIT, Massachusetts Institute of Technology)

  • Margaret Cunniff

    (Broad Institute of MIT and Harvard
    McGovern Institute for Brain Research, MIT, Massachusetts Institute of Technology)

  • Feng Zhang

    (Broad Institute of MIT and Harvard
    McGovern Institute for Brain Research, MIT, Massachusetts Institute of Technology)

Abstract

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.

Suggested Citation

  • Le Cong & Ruhong Zhou & Yu-chi Kuo & Margaret Cunniff & Feng Zhang, 2012. "Comprehensive interrogation of natural TALE DNA-binding modules and transcriptional repressor domains," Nature Communications, Nature, vol. 3(1), pages 1-6, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1962
    DOI: 10.1038/ncomms1962
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    Cited by:

    1. Hua Wan & Jian-ping Hu & Kang-shun Li & Xu-hong Tian & Shan Chang, 2013. "Molecular Dynamics Simulations of DNA-Free and DNA-Bound TAL Effectors," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-12, October.

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