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Deciphering TAL effectors for 5-methylcytosine and 5-hydroxymethylcytosine recognition

Author

Listed:
  • Yuan Zhang

    (Peking University
    Peking University)

  • Lulu Liu

    (Peking University)

  • Shengjie Guo

    (Peking University
    Peking University
    Peking University)

  • Jinghui Song

    (Peking University)

  • Chenxu Zhu

    (Peking University)

  • Zongwei Yue

    (Peking University)

  • Wensheng Wei

    (Peking University
    Peking University
    Peking University
    Peking University)

  • Chengqi Yi

    (Peking University
    Peking University
    Peking University)

Abstract

DNA recognition by transcription activator-like effector (TALE) proteins is mediated by tandem repeats that specify nucleotides through repeat-variable diresidues. These repeat-variable diresidues form direct and sequence-specific contacts to DNA bases; hence, TALE–DNA interaction is sensitive to DNA chemical modifications. Here we conduct a thorough investigation, covering all theoretical repeat-variable diresidue combinations, for their recognition capabilities for 5-methylcytosine and 5-hydroxymethylcytosine, two important epigenetic markers in higher eukaryotes. We identify both specific and degenerate repeat-variable diresidues for 5-methylcytosine and 5-hydroxymethylcytosine. Utilizing these novel repeat-variable diresidues, we achieve methylation-dependent gene activation and genome editing in vivo; we also report base-resolution detection of 5hmC in an in vitro assay. Our work deciphers repeat-variable diresidues for 5-methylcytosine and 5-hydroxymethylcytosine, and provides tools for TALE-dependent epigenome recognition.

Suggested Citation

  • Yuan Zhang & Lulu Liu & Shengjie Guo & Jinghui Song & Chenxu Zhu & Zongwei Yue & Wensheng Wei & Chengqi Yi, 2017. "Deciphering TAL effectors for 5-methylcytosine and 5-hydroxymethylcytosine recognition," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00860-6
    DOI: 10.1038/s41467-017-00860-6
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