Direct, programmable detection of epigenetic DNA cytosine modifications using TAL effectors

摘要

Methods for the differentiation of a 5-hydroxymethyl modification of a cytosine residue of interest in a nucleic acid molecule from (i) a 5-methyl modification of the cytosine residue of interest or (ii) an unmodified cytosine residue of interest, the methods making use of the capability of transcription-activator-like effector (TALE) proteins to preferentially bind with strong affinity to nucleic acid sequences containing non-modified cytosine residues or 5-methyl modified cytosine residues, and to bind, if at all, with only strongly reduced affinity to nucleic acid sequences containing 5-hydroxymethyl modified cytosine residues. The present invention further relates to respective uses of TALE proteins for the differentiation of a 5-hydroxymethyl modification of a cytosine residue of interest in a nucleic acid molecule from (i) a 5-methyl modification of the cytosine residue of interest or (ii) the unmodified cytosine residue of interest.