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

Yuan Zhang, Lulu Liu, Shengjie Guo, Jinghui Song, Chenxu Zhu, Zongwei Yue, Wensheng Wei () and Chengqi Yi ()
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Yuan Zhang: Peking University
Lulu Liu: Peking University
Shengjie Guo: Peking University
Jinghui Song: Peking University
Chenxu Zhu: Peking University
Zongwei Yue: Peking University
Wensheng Wei: Peking University
Chengqi Yi: Peking University

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00860-6

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