Deciphering TAL effectors for 5-methylcytosine and 5-hydroxymethylcytosine recognition. Academic Article uri icon

Overview

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.Transcription activator-like effector proteins recognise specific DNA sequences via tandem repeats. Here the authors demonstrate TALEs can recognise the methylated bases 5mC and 5hmC, enabling them to detect epigenetic modifications.

publication date

  • October 12, 2017

Research

keywords

  • 5-Methylcytosine
  • DNA
  • Transcription Activator-Like Effectors

Identity

PubMed Central ID

  • PMC5638953

Scopus Document Identifier

  • 85031280845

Digital Object Identifier (DOI)

  • 10.1007/978-1-4939-2932-0_5

PubMed ID

  • 29026078

Additional Document Info

volume

  • 8

issue

  • 1