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Achieving Single‐Nucleotide Resolution of 5‐Methylcytosine Detection with TALEs

We report engineered transcription‐activator‐like effectors (TALEs) as the first DNA‐binding molecules that detect 5‐methylcytosine (mC) at single‐nucleotide resolution with fully programmable sequence selectivity. This is achieved by a design strategy such that a single cytosine (C) in a DNA sequence is selectively interrogated for its mC‐modification level by targeting with a discriminatory TALE repeat; other Cs are ignored by targeting with universal‐binding TALE repeats.